diff --git a/cpp/cmake_modules/ThirdpartyToolchain.cmake b/cpp/cmake_modules/ThirdpartyToolchain.cmake
index 4eab2ab20869..1b5ee9a20e86 100644
--- a/cpp/cmake_modules/ThirdpartyToolchain.cmake
+++ b/cpp/cmake_modules/ThirdpartyToolchain.cmake
@@ -2567,7 +2567,11 @@ if(ARROW_MIMALLOC)
       "-DCMAKE_C_FLAGS=${MIMALLOC_C_FLAGS}"
       "-DCMAKE_INSTALL_PREFIX=${MIMALLOC_PREFIX}"
       -DMI_INSTALL_TOPLEVEL=ON
+      # Don't override default malloc
       -DMI_OVERRIDE=OFF
+      -DMI_OSX_INTERPOSE=OFF
+      -DMI_OSX_ZONE=OFF
+      # Allow usage through dlopen (i.e. when libarrow.so itself is dlopen'ed)
       -DMI_LOCAL_DYNAMIC_TLS=ON
       -DMI_BUILD_OBJECT=OFF
       -DMI_BUILD_SHARED=OFF
@@ -2575,6 +2579,14 @@ if(ARROW_MIMALLOC)
       # GH-47229: Force mimalloc to generate armv8.0 binary
       -DMI_NO_OPT_ARCH=ON)
 
+  if(APPLE)
+    list(APPEND
+         MIMALLOC_CMAKE_ARGS
+         # GH-50428: Make sure several mimalloc instances can cohabit in the same process
+         # (also https://github.com/microsoft/mimalloc/issues/1327#issuecomment-4964140817)
+         -DMI_TLS_MODEL_LOCAL=ON)
+  endif()
+
   externalproject_add(mimalloc_ep
                       ${EP_COMMON_OPTIONS}
                       URL ${MIMALLOC_SOURCE_URL}
diff --git a/cpp/thirdparty/versions.txt b/cpp/thirdparty/versions.txt
index c6f4b01a717c..ff05b6bbae93 100644
--- a/cpp/thirdparty/versions.txt
+++ b/cpp/thirdparty/versions.txt
@@ -80,8 +80,8 @@ ARROW_JEMALLOC_BUILD_VERSION=5.3.0
 ARROW_JEMALLOC_BUILD_SHA256_CHECKSUM=2db82d1e7119df3e71b7640219b6dfe84789bc0537983c3b7ac4f7189aecfeaa
 ARROW_LZ4_BUILD_VERSION=v1.10.0
 ARROW_LZ4_BUILD_SHA256_CHECKSUM=537512904744b35e232912055ccf8ec66d768639ff3abe5788d90d792ec5f48b
-ARROW_MIMALLOC_BUILD_VERSION=v3.3.1
-ARROW_MIMALLOC_BUILD_SHA256_CHECKSUM=42c16914168ac6741eeb407e83b93a12b2b7ee25a7e14e6b4807fab8b577a540
+ARROW_MIMALLOC_BUILD_VERSION=v3.4.1
+ARROW_MIMALLOC_BUILD_SHA256_CHECKSUM=37107a52c16baa80c5f74861dddda7b27bb9949e41a6637691867a94c88ca446
 ARROW_NLOHMANN_JSON_BUILD_VERSION=v3.12.0
 ARROW_NLOHMANN_JSON_BUILD_SHA256_CHECKSUM=4b92eb0c06d10683f7447ce9406cb97cd4b453be18d7279320f7b2f025c10187
 ARROW_OPENTELEMETRY_BUILD_VERSION=v1.21.0