Aging and osteoarthritis (OA) are associated with a high risk of muscle mass loss, which can lead to physical disability. This study investigated the effectiveness of protein supplementation combined with exercise training (PS + ET) in improving muscle mass and functional outcomes in older adults with lower-limb OA. A comprehensive search of online databases was performed to identify randomized controlled trials (RCTs) on the effectiveness of PS+ET in older adults with hip or knee OA. Meta-analysis and risk of bias assessment of the included RCTs were conducted. Six RCTs were included in this systemic review; they had a median (range/total) Physiotherapy Evidence Database (PEDro) score of 7 (6 to 9) out of 10, respectively. Five RCTs that enrolled patients who underwent total joint replacement were included in this meta-analysis. The PS+ET group exhibited significant improvements in muscle mass (standard mean difference (SMD) 1.13, p < 0.00001), pain (SMD 1.36, p < 0.00001), and muscle strength (SMD 0.44, p = 0.04). Our findings suggest that PS+ET improves muscle mass, muscle strength, and functional outcomes and reduces pain in older adults with lower-limb OA, particularly in those who have undergone total joint replacement.

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