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Astaxanthin (ATX), a naturally occurring carotenoid, exhibits notable neuroprotective properties, including anti-inflammatory effects and regulation of neurotrophic factors. This study investigates the fundamental processes by which astaxanthin facilitates the repair of peripheral nerve injuries. Our experiments with in vivo and in vitro models reveal that astaxanthin treatment induces a shift from M1 to M2 microglial polarization and attenuates the inflammatory response in Schwann cells. However, these beneficial effects are negated by the inhibition of the STAT6-PPARγ pathway. Furthermore, astaxanthin administration mitigated gastrocnemius muscle atrophy in rats with peripheral nerve injuries and enhanced axonal regeneration and myelination. Notably, an increase in neovascularization was also observed post-treatment. In summary, astaxanthin significantly promotes nerve regeneration following peripheral nerve injury, highlighting its potential therapeutic value and underscoring the need for further clinical investigations.