Objective(s): To investigate the physicochemical properties, in vitro efficacy, and in vivo therapeutic potential of novel tree turmeric root and nano-hydroxyapatite (TRE@NHA) composites in mitigating Materials and Methods: TRE@NHA composites were synthesized and characterized using FTIR, XRD, TGA, and HRTEM. In vitro studies using PC12 cells assessed cytotoxicity, anti-inflammatory effects, and neuroprotective properties. An in vivo rat model of CIPN was established using paclitaxel (PTX). Behavioral assessments, histopathological analysis, and oxidative stress markers were evaluated in sciatic nerve tissues. Results: TRE@NHA composites demonstrated successful integration of TRE into the NHA matrix. In vitro studies revealed significant anti-inflammatory and neuroprotective effects of TRE@NHA-2, particularly in suppressing cytokine production, enhancing cell viability, and mitigating oxidative stress. In vivo, TRE@NHA-2 effectively alleviated PTX-induced neuropathic pain, reduced neuronal damage, and exhibited potent antioxidant properties. Conclusion: This study demonstrates the successful development and characterization of novel TRE@ NHA composites. The findings strongly suggest that TRE@NHA-2 possesses promising therapeutic potential for mitigating CIPN due to its anti-inflammatory, antioxidant, and neuroprotective properties.