Seventy patients with mild to moderate knee osteoarthritis and a BMI of 25–40 kg/m² were randomized to receive Saccharomyces boulardii probiotic capsules (n=35) or placebo (n=35) for 12 weeks. The primary outcome was change in pain intensity measured by the WOMAC pain score. Secondary outcomes included VAS pain scores, acetaminophen intake, serum hs-CRP, MDA, TAC, and quality of life scores. Outcomes were assessed at baseline and after 12 weeks. Overall, the results of the study revealed that probiotic supplementation led to significantly greater reductions in WOMAC pain scores, VAS pain, acetaminophen use, hs-CRP, and MDA compared to placebo. S. boulardii also improved select quality of life measures. These findings suggest that S. boulardii supplementation can effectively reduce pain and inflammation in overweight/obese KOA patients.