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Background: Emerging evidence suggests that body weight misperception may be associated with psychological distress among people in developed countries. Participating in physical activity (PA) may negate the association between weight misperception and psychological distress given the well-known benefits of PA on psychological health. This study examined the role of PA in associations between body weight misperception and psychological distress among young South Korean adults., Methods: Data from individuals aged 20 to 39 years who participated in the Fifth Korean National Health and Nutrition Examination Surveys 2010-2012 ( N  = 6055) was included in the logistic regressions., Results: The proportions of the respondents under- and over-perceiving their body weight were 66.9% and 0.8% among men and 16.3% and 15.6% among women respectively. A moderating effect of PA participation was observed on the relationship between body weight over-perception and depressed mood (Odds Ratio [OR] = 0.55; 95% Confidence Intervals [95% CI] = 0.34, 0.89). Among individuals who did not meet the recommended vigorous-intensity PA (≥ 20 min/session and ≥ 3 day/week), body weight over-perception was associated with depressed mood (OR = 1.71, 95% CI = 1.19, 2.46) compared to the accurate-perception group. However, no association was observed among those who met the recommended vigorous-intensity PA (OR = 1.52, 95% CI = 0.45, 5.22). Similar patterns were found among physically active versus inactive individuals (recommended walking not met: OR = 2.02, 95% CI = 1.29, 3.15; recommended walking met: OR = 1.28, 95% CI = 0.66, 2.49; muscular strengthening exercises for < 2 day/week: OR = 1.74, 95% CI = 1.21, 2.51; muscular strengthening exercises for ≥ 2 day/week: OR = 1.38, 95% CI = 0.37, 5.14). No relationship existed between body weight over-perception and depressed mood after adjusting for PA., Conclusions: Participating in regular PA may buffer a potential negative impact of body weight over-perception on depressive mood.