Obesity in middle-aged women is commonly linked with chronic inflammation, psychological stress, and poor sleep quality. Holistic, non-pharmacological approaches such as yoga and mindfulness may offer multidimen- sional benefits. This randomized controlled trial investigated the impact of a 12-week yoga and mindfulness meditation program on psychological stress, inflammatory markers, and sleep quality in obese women. Sixty participants (BMI≥30 kg/m²; age 40–55) were randomly assigned to an intervention group (n=30) or a con- trol group (n=30). The intervention group underwent thrice-weekly sessions (60 minutes each) combining yoga postures, breathing exercises, and mindfulness meditation. The control group maintained usual routines. Outcomes assessed at baseline and post-intervention included perceived stress (PSS-10), depression symp- toms (BDI-II), sleep quality (PSQI), erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein (hs-CRP). After 12 weeks, the intervention group showed significant reductions in perceived stress (−38.7%, p<0.001), depression symptoms (−42.3%, p<0.001), and sleep disturbances (−36.9%, p=0.002) compared to controls. Inflammatory markers also improved significantly: ESR decreased by 26.7% (p=0.007) and hs-CRP by 31.5% (p=0.003). No significant changes were observed in the control group. A structured yoga and mindful- ness meditation program significantly improved psychological and physiological outcomes in middle-aged obese women. These findings support incorporating mind-body interventions in obesity management to ad- dress both mental and physical health.