Background: South Asian Indian immigrants residing in the United States are at high risk of cardiovascular disease (prevalence ≥35%), diabetes (prevalence 45.4%), and stroke (prevalence 26.5%). This study examined the effect of culturally relevant physical activity interventions on the improvement of physiological measures and average daily steps in at-risk midlife South Asian Indian immigrant women. Methods: In this 2-arm interventional research design, the dance (n = 25) and the motivational phone calls group (n = 25), attended social cognitive theory–based motivational workshops every 2 weeks for the first 12 weeks. Data for weight, waist circumference, blood pressure, blood sugar, cholesterol level, and 12-lead electrocardiogram were collected at the baseline, 12 weeks, and 24 weeks. Results: Significant differences were seen in body weight (F_2,94 = 4.826, P = .024; ${\eta }_{\mathrm{p}}^2=.093$), waist circumference (F_2,92 = 7.496, P = .001; ${\eta }_{\mathrm{p}}^2=.140$), systolic blood pressure (F_2,94 = 19.865, P = .000; ${\eta }_{\mathrm{p}}^2=.2970$), triglyceride (F_2,94 = 11.111, P = .000; ${\eta }_{\mathrm{p}}^2=.191$), cholesterol (F_2,94 = 8.925, P = .001; ${\eta }_{\mathrm{p}}^2=.160$), blood sugar level (F_2,94 = 8.851, P = .000; ${\eta }_{\mathrm{p}}^2=.158$), and average daily steps across both intervention groups over time (F_2,96 = 30.94, P = .000; ${\eta }_{\mathrm{p}}^2=.392$). Conclusion: Culturally relevant motivational workshops with Indian dance and walking are an innovative approach to increasing lifestyle physical activity among South Asian Indian immigrant women.