Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that affects joints of hands and feet and introduces injury in secondary organs such as cardiac tissue. In the present study, we induced RA in male Balb/c mice (CAIA) using collagen-antibody cocktail (C-Ab) and lipopolysaccharide intraperitoneal injections. Induction of RA in the animals was detected through the loss of body weight, food, and water consumption, pedal edema, increased arthritis score of the paw and ankle, increase in radiological and histological lesion score of ankle and knee joints and enhanced pain perception in the C-Ab induced RA animals. Ashwashila is a herbo-mineral medicine from Indian Ayurvedic system. Human equivalent doses of Ashwashila (ASHW) and standard of care, Methotrexate were given to the CAIA animals for two weeks. ASHW treatment significantly reversed the effect of C-Ab with reduced pedal edema, arthritis score, radiological and histological lesion scores in ankle-joint, knee-joint and articular cartilage, reduced pain perception. These effects were comparable with the Methotrexate treatment. In human monocytic (THP-1) cells, ASHW was found to be biocompatible at in-vitro test doses. The anti-arthritis mechanism of action for ASHW was established through the suppression of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α; and upstream regulator, NF-κB. Taken together, we show the pre-clinical efficacy of ASHW in reducing RA associated symptoms by controlling inflammation and suggest it as a potential therapeutic candidate for rheumatoid arthritis.