diff --git a/CHANGELOG.md b/CHANGELOG.md
index 95b59d87e56..be51681e5c5 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -50,6 +50,7 @@ Compatibility:
 
 Performance:
 
+* Speedup some C extensions like `sqlite3`, `trilogy` and `json` by 2 to 3 times by using the Panama NFI backend for faster upcalls in JVM mode (@eregon).
 * Optimize encoding negotiation for ASCII-compatible encodings (@eregon, @andrykonchin).
 
 Changes:
diff --git a/lib/truffle/truffle/cext.rb b/lib/truffle/truffle/cext.rb
index 61fa786b680..9c19ade6d3a 100644
--- a/lib/truffle/truffle/cext.rb
+++ b/lib/truffle/truffle/cext.rb
@@ -190,7 +190,20 @@ def self.init_libtrufflerubytrampoline(libtrampoline)
 
     init_functions = libtrampoline[:rb_tr_trampoline_init_functions]
     init_functions = Primitive.interop_eval_nfi('(env,(string):pointer):void').bind(init_functions)
-    if Truffle::Boot.get_option 'cexts-panama' and Primitive.vm_java_version >= 22 and !TruffleRuby.native?
+
+    panama = Truffle::Boot.get_option('cexts-panama') && Primitive.vm_java_version >= 22 && !TruffleRuby.native?
+    if panama
+      # Check if the Panama backend is available, it might not be when embedding TruffleRuby
+      rb_tr_invoke = LIBTRUFFLERUBY['rb_tr_invoke']
+      begin
+        keep_alive << rb_tr_invoke.createNativeClosure('panama')
+      rescue Polyglot::ForeignException => e
+        warn "warning: the Panama Truffle NFI backend for running C extensions faster is not available (#{e.message}). Add 'org.graalvm.truffle:truffle-nfi-panama' to Maven dependencies to resolve or use '--ruby.cexts-panama=false' to ignore."
+        panama = false
+      end
+    end
+
+    if panama
       init_functions.call(-> name {
         closure = LIBTRUFFLERUBY[name].createNativeClosure('panama')
         keep_alive << closure
diff --git a/src/main/java/org/truffleruby/options/Options.java b/src/main/java/org/truffleruby/options/Options.java
index c9454214d1b..03a71a2ee8c 100644
--- a/src/main/java/org/truffleruby/options/Options.java
+++ b/src/main/java/org/truffleruby/options/Options.java
@@ -107,7 +107,7 @@ public final class Options {
     public final boolean CEXTS;
     /** --cexts-lock=true */
     public final boolean CEXT_LOCK;
-    /** --cexts-panama=false */
+    /** --cexts-panama=true */
     public final boolean CEXTS_PANAMA;
     /** --options-log=false */
     public final boolean OPTIONS_LOG;
diff --git a/src/options.yml b/src/options.yml
index f9c2f78a0c2..82dbfb693d0 100644
--- a/src/options.yml
+++ b/src/options.yml
@@ -132,7 +132,7 @@ EXPERT:
     # C extension options
     CEXTS: [cexts, boolean, true, Enable use of C extensions]
     CEXT_LOCK: [cexts-lock, boolean, true, Use a Global Lock when running C extensions]
-    CEXTS_PANAMA: [cexts-panama, boolean, false, 'Use Panama for native to Ruby calls in C extensions. Only available in --jvm mode on JDK 22+.']
+    CEXTS_PANAMA: [cexts-panama, boolean, true, 'Use Panama for native to Ruby calls in C extensions. Only available in --jvm mode on JDK 22+.']
 
     # Debugging the values of options
     OPTIONS_LOG: [options-log, boolean, false, Log the final value of all options]
diff --git a/src/shared/java/org/truffleruby/shared/options/OptionsCatalog.java b/src/shared/java/org/truffleruby/shared/options/OptionsCatalog.java
index b30be90715c..adb40077bff 100644
--- a/src/shared/java/org/truffleruby/shared/options/OptionsCatalog.java
+++ b/src/shared/java/org/truffleruby/shared/options/OptionsCatalog.java
@@ -71,7 +71,7 @@ public final class OptionsCatalog {
     public static final OptionKey<Boolean> BACKTRACE_ON_NEW_FIBER_KEY = new OptionKey<>(false);
     public static final OptionKey<Boolean> CEXTS_KEY = new OptionKey<>(true);
     public static final OptionKey<Boolean> CEXT_LOCK_KEY = new OptionKey<>(true);
-    public static final OptionKey<Boolean> CEXTS_PANAMA_KEY = new OptionKey<>(false);
+    public static final OptionKey<Boolean> CEXTS_PANAMA_KEY = new OptionKey<>(true);
     public static final OptionKey<Boolean> OPTIONS_LOG_KEY = new OptionKey<>(false);
     public static final OptionKey<Boolean> LOG_LOAD_KEY = new OptionKey<>(false);
     public static final OptionKey<Boolean> LOG_AUTOLOAD_KEY = new OptionKey<>(false);
diff --git a/src/test-embedding/java/org/truffleruby/test/embedding/ContextPermissionsTest.java b/src/test-embedding/java/org/truffleruby/test/embedding/ContextPermissionsTest.java
index 645382ad033..ac445091b91 100644
--- a/src/test-embedding/java/org/truffleruby/test/embedding/ContextPermissionsTest.java
+++ b/src/test-embedding/java/org/truffleruby/test/embedding/ContextPermissionsTest.java
@@ -77,6 +77,13 @@ public void testRequireGem() {
         }
     }
 
+    @Test
+    public void testRequireCExtension() {
+        try (Context context = Context.newBuilder("ruby").allowIO(IOAccess.ALL).allowNativeAccess(true).build()) {
+            Assert.assertEquals("Etc", context.eval("ruby", "require 'etc'; Etc.to_s").asString());
+        }
+    }
+
     @Test
     public void testThreadsNoNative() throws Throwable {
         // The ruby.single_threaded option needs to be set because --single-threaded defaults to --embedded.