Thirty-six randomized controlled trials including 3,048 patients who underwent primary unilateral total knee arthroplasty were included in this systematic review and meta-analysis comparing perioperative glucocorticoids vs. standard care. Pooled outcomes of interest included postoperative pain (VAS scores), morphine consumption, inflammatory cytokine levels (CRP and IL-6), range of motion, adverse effects (PONV, wound infection, venous thrombosis), and length of hospital stay. The analysis showed that glucocorticoids significantly reduced short-term pain scores, morphine consumption, and CRP and IL-6 levels without increasing the risk of wound infection or venous thrombosis. These findings suggest that perioperative glucocorticoids can effectively manage pain and inflammation after TKA without significant adverse effects.