Osteoarthritis (OA) is characterized by the breakdown of cartilage in joints. Most currently-used drugs to treat OA induce gastrointestinal troubles and renal impairment. The current study investigated the alleviative effects of the ethanolic crude extract of Bauhinia variegata (BV) leaves on monosodium iodoacetate (MIA)-induced OA. Ten groups of male Wistar albino rats (Rattus norvegicus; 5 rats/group) were randomly allotted into the control group that (G1) received distilled water; groups treated orally/daily with 200, 400, or 600 mg of BV extract/kg body weight, or the reference drug (250 mg glucosamine sulfate/kg body weight) for 4 weeks (G2-G5, respectively); group treated with 40 mg MIA/mL once by intra-articular injection (G6); and groups treated with MIA + the different doses of BV extract or the reference drug (orally/daily for 4 weeks) after 4 weeks of MIA injection (G7-G10, respectively). The results showed significant increases in serum calcium and phosphorus levels, and significant decreases in the activity of serum alkaline phosphatase, the levels of serum interleukin-6, prostaglandin E2, leptin, and type II collagen, as well as the levels of cyclooxygenase 2 and inducible nitric oxide synthase in knee joints, in the MIA groups treated with BV extract (in a dose-dependent manner) compared with the MIA group. The X-ray imaging showed a significant increase in joint space in the MIA groups treated with the high doses of BV extract compared with the MIA group. The present study suggested that BV extract may be promising in the treatment of OA.