Chronic inflammation, particularly in arthritis, affects millions worldwide, leading to pain, reduced mobility, and diminished quality of life. Conventional therapies such as NSAIDs, corticosteroids, and biologics provide symptomatic relief, but are associated with adverse effects like gastrointestinal issues, cardiovascular risks, and increased susceptibility to infections. This highlights the need for safer, alternative therapeutic strategies. Plant-based therapies have gained attention due to their potential antioxidant and anti-inflammatory properties. In this context, the present study investigated the antioxidant and anti-arthritic potential of Micrococca mercurialis stem (MMS) extract. Bioactive compounds, including total phenolics (TPC) and flavonoids (TFC), were quantified using standard assays. Their antioxidant capacity was evaluated through DPPH, ABTS, and total antioxidant capacity assays. Anti-arthritic efficacy was assessed in a Complete Freund’s Adjuvant (CFA)-induced arthritis model in rats. MMS extract was administered at doses of 200 and 400 mg/kg and compared with the standard drug, indomethacin. A methanolic extract of MMS showed significant bioactive content, with TPC and TFC values of 112.12 ± 4.47 mg GAE/g and 12.54 ± 0.52 mg QE/g, respectively. The ABTS radical scavenging activity (IC₅₀ = 62.85 ± 2.25 µg/mL) was stronger than DPPH activity (88.16 ± 2.01 µg/mL) and comparable to gallic acid. In the anti-arthritic model, MMS extract exhibited dose-dependent effects. The 400 mg/kg dose showed comparable efficacy to indomethacin (10 mg/kg) at all time points (days 4, 8, 14, and 21), with significant paw volume reduction (p < 0.001). Hematological parameters such as RBC, WBC, Hb, and ESR, elevated due to inflammation, were normalized in the high-dose group. The methanol extract of Micrococca mercurialis stem demonstrated potent anti-inflammatory and antioxidant activities, suggesting its potential as a source of novel therapeutic agents for inflammatory conditions.