This study aimed to comparatively evaluate the protective effects of nanocurcumin and Black seed against acute arthritis induced by bacterial LPS in pigeons and compare these effects with the standard NSAID, Diclofenac. A total of 35 pigeons were divided into five groups: Sham control (T1), LPS-induced arthritis control (T2), and treatment groups receiving Diclofenac (T3), Black seed (T4), or nanocurcumin (T5) after LPS challenge. Arthritis was induced by intra-articular LPS injection. At 48 hours post-injection, synovial fluid was collected and histopathological evaluation was performed. In the sections, congestion, hyperplastic reaction of synovial components including reactive fibrosis, congestion, and hypertrophy of chondrocytes was recognized. Histopathologic evaluation revealed that group T4 demonstrated a severe inflammatory reaction while mesenchymal and synovial reaction of groups T3 and T5 obtained the total score of 6. Systemically, LPS significantly elevated serum epinephrine and corticosterone levels. Diclofenac treatment resulted in the most significant reduction in both epinephrine and corticosterone levels compared to the natural supplement groups. In the synovial fluid, the positive control showed the highest concentrations of TNF-α and IL-6. Diclofenac demonstrated the strongest suppression of TNF-α, while both Black seed and nanocurcumin significantly reduced both TNF-α and IL-6 compared to the untreated group. Nanocurcumin demonstrated a significant reduction in corticosterone than Black seed. Diclofenac exhibited the most potent anti-inflammatory effect, However, both nanocurcumin and Black seed provided significant therapeutic benefits in mitigating LPS-induced acute arthritis, suggesting their potential as viable natural adjuncts in avian inflammatory disease management, particularly when considering the toxicity profile of NSAIDs.