Background: Health risks among informal caregivers have received inadequate attention in low and middle income countries. We examined cross-sectional data from 28611 adults 18 years and older in Ghana, India, Mexico, Russia and South Africa in the WHO Study on Global AGEing and Adult Health (SAGE) to examine gender differences in informal caregiving and wellbeing. Methods: Wellbeing was measured by self-rated health, difficulties with tasks, self-reported and diagnosed depression and anxiety. Informal caregiving was specific to adults and constructed as categorical variable with the respondent as: the main caregiver, non-caregiver but an adult in the household needs care, and no-one ill in the household; multinomial gender-stratified regression models assessed adjusted relative risk ratios (ARRRs). Results: Female caregivers were more likely to report moderate difficulties with life tasks [ARRR = 1.45 (95% CI: 1.01, 2.08)], feel mild-moderate anxiety [ARRR = 1.64 (95% CI: 1.22, 2.22)], and report feeling severely depressed [ARRR = 1.86 (95% CI: 1.28, 2.69)] compared to female non-caregivers. Even when women were not caregivers, having someone ill at home was associated with extreme difficulties with life tasks [ARRR = 2.32 (95% CI: 1.33, 4.04)]. Male caregivers, compared to no-one ill in the household, were more likely to report mild-moderate anxiety [ARRR = 1.8 (95% CI: 1.2, 3.7)] and severe-extreme anxiety [ARRR = 2.22 (95% CI: 1.07, 4.6)]. Conclusions: Caregiving for older adults results in greater health burdens, particularly mental health, for both women and men, though evidence shows that these burdens may be prominent and manifest in more diverse ways for women relative to men.