The study aimed to investigate the potential anti-arthritic effects of methanolic aerial extract of the plant Strelitzia reginae (MSRA), because of its potential anti-arthritic effects.The research utilised Wistar albino rats, and all groups except the control group had arthritis in their right hind paws caused by 0.1 ml of CFA (Complete Freund’s adjuvant) emulsion. For 21 days, all rats (except those in the normal and arthritic groups) were administered the extract at doses of 600, 300, and 150 mg/kg/day in conjunction with 10 mg/kg of piroxicam. By enhancing biochemical markers, reducing paw edoema, and reestablishing immunological organs and body weight, the extract shown substantial effects. Polymerase chain reaction (PCR) results demonstrated a significant decrease in receptor activator of nuclear factor kappa-beta ligand (RANKL), interlukin-17a (IL-17a), tumour necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ). The study also found that when polyarthritic groups were treated with dosages of MSRA, the expression of osteoprotegrin (OPG) and IL-4 was upregulated. Around 600 mg/kg/day, the highest levels of OPG (1.24 ± 0.025 ng/ml) and IL-4 (80.31 ± 0.23-fold) were seen. The levels of catalase (CAT) and superoxide dismutase (SOD) increased (p < 0.05) in the groups treated with 600 mg/kg MSRA and piroxicam, while malondialdehyde (MDA) decreased.