This study investigates the therapeutic potential of poly(p-coumaric acid) nanoparticles (PCA NPs) in alleviating temporomandibular joint osteoarthritis (TMJOA). PCA NPs, synthesized from p-coumaric acid, exhibit superior antioxidant and anti-inflammatory properties compared to hyaluronic acid (HA), a commonly used viscosupplementation. In a rat model of TMJOA, PCA NPs showed long-term efficacy in reducing cartilage degradation, subchondral bone erosion, and chronic pain. The nanoparticles enhanced cell proliferation and matrix synthesis while reducing inflammation, oxidative stress, and chondrocyte ferroptosis. Mechanistically, PCA NPs improved chondrocyte viability, reduced inflammation, and inhibited matrix degradation by modulating key pathways and proteins involved in ferroptosis. Overall, the study demonstrates that PCA NPs are a promising, multifunctional therapeutic approach for TMJOA, offering a stable and effective way to target both inflammation and oxidative stress.This study investigates the therapeutic potential of poly(p-coumaric acid) nanoparticles (PCA NPs) in alleviating temporomandibular joint osteoarthritis (TMJOA). PCA NPs, synthesized from p-coumaric acid, exhibit superior antioxidant and anti-inflammatory properties compared to hyaluronic acid (HA), a commonly used viscosupplementation. In a rat model of TMJOA, PCA NPs showed long-term efficacy in reducing cartilage degradation, subchondral bone erosion, and chronic pain. The nanoparticles enhanced cell proliferation and matrix synthesis while reducing inflammation, oxidative stress, and chondrocyte ferroptosis. Mechanistically, PCA NPs improved chondrocyte viability, reduced inflammation, and inhibited matrix degradation by modulating key pathways and proteins involved in ferroptosis. Overall, the study demonstrates that PCA NPs are a promising, multifunctional therapeutic approach for TMJOA, offering a stable and effective way to target both inflammation and oxidative stress.