Background: The objective of this study was to analyze the effectiveness of a mindfulness-based intervention program for the promotion of well-being and health in family caregivers. Methods: The participants were 111 family women caregivers aged between 33 and 75 years old. This was a double-blinded randomized controlled trial. The mindfulness intervention program lasted 12 weeks. The experimental group underwent mindfulness and acceptance-based interventions (MABIs). The control group performed physical activity training. Results: A cross-lagged panel analysis was computed with the two waves of health, well-being, burden and resilience and age in years and intervention as predictors. The cross-lagged path model fit well χ² (8) = 7.179, p = 0.51, root mean square error of approximation (RMSEA) = 0.00, comparative fit index (CFI)= 1.00, standardized root mean square residual (SRMR) = 0.05. The mindfulness intervention program was a significant predictor accounting for decreasing health problems (β = −0.292, p < 0.01) and burden (β = −0.190, p < 0.01) and increasing well-being (β = 0.107, p < 0.05) at post-test. Conclusions: Mindfulness-based intervention programs are effective in coping with the burden of family caregivers and, in turn, in promoting resilience, well-being and health among caregivers. Our findings encourage clinical uses of mindfulness interventions to promote health.