Introduction: A woman’s risk of stroke increases exponentially after menopause, and even a mild ischemic episode can result in increased frailty. Studies performed in laboratory animals and humans support the hypothesis that whole body vibration (WBV) reduces or reverses pathological remodeling of bone and lessens frailty-related physiological deterioration. Using a rodent model of stroke, we have examined whether WBV reduces inflammation and post-ischemic damage and improves motor function in reproductively senescent (RS) female rats. Methods: The estrous cycles of retired breeder Sprague–Dawley female rats (9–12 months; n = 4-6) were monitored for 14-20 days by daily vaginal smears. Rats that remained in constant diestrous were considered RS, exposed to transient middle cerebral artery occlusion (tMCAO; 60 min) and randomly assigned to either WBV or control groups. Animals placed in the WBV (40 Hz) group underwent 30 days of WBV treatment performed twice daily for 15 min each session for 5 days each week. During the treatment period, we tested motor function using a rotarod test intermittently after tMCAO. Animals were sacrificed on 30th day of WBV treatment and brain tissue was harvested for histopathological and inflammasome protein analysis performed by western blotting. Results: WBV decreased protein levels of caspase-1, ASC and IL-1 β by 88% (p < 0.05), 57% (p < 0.05) and 148% (p < 0.05) in the peri-infarct area as compared to control-treated group. The rotarod test scores from the WBV treatment group were significantly higher than the control group on day 30 (p < 0.05), suggesting a significant improvement in functional activity of the WBV group. The histopathological assessment demonstrated a significant reduction in infarct volume in a mild-stroke model following WBV treatment as compared to control rats. We observed 56% reduction in infarct volume of WBV treated rats as compared to control. In parallel, we also monitored neurological deficit of rats that were exposed to WBV/control treatment after tMCAO. Conclusion: The post-ischemic WBV intervention reduces brain damage and frailty in RS female rats, suggesting that WBV may be a potential therapy to reduce post-ischemic frailty and improve functional and cognitive outcomes after stroke in women.