•Little is known about dietary pesticide exposure profiles and BW change.•The lower dietary exposure to synthetic pesticides the lower weight gain in women.•The lower weight gain is observed in premenopausal women only.•The higher dietary exposure to a pesticide mixture the higher weight loss in men. Pesticides cause a wide range of deleterious health effects, including metabolic disorders. Little is known about the effects of dietary pesticide exposure on body weight (BW) change in the general population. We aimed to investigate the role of dietary pesticide exposure in BW change among NutriNet-Santé participants, focusing on potential sexual dimorphism. Participants completed a Food Frequency Questionnaire (2014), assessing conventional and organic food consumption. Dietary exposure from plant foods of 25 commonly used pesticides was estimated using a residue database, accounting for agricultural practices (conventional and organic). Exposure profiles based on dietary patterns were computed using Non-negative Matrix Factorization (NMF). Mixed models were used to estimate the associations between BW change and exposure to pesticide mixtures, overall and after stratification by sex and menopausal status. The final sample included 32,062 participants (8,211 men, 10,637 premenopausal, and 13,214 postmenopausal women). The median (IQR) follow-up was 7.0 (4.4; 8.0) years. Four pesticides profiles were inferred. Overall, men and postmenopausal women lost BW during follow-up, whereas premenopausal women gained BW. Higher exposure to NMF3, reflecting a lower exposure to synthetic pesticides, was associated with a lower BW gain, especially in premenopausal women (β(95 %CI) = -0.04 (-0.07; 0) kg/year, p = 0.04). Higher exposure to NMF2, highly positively correlated with a mixture of synthetic pesticides (azoxystrobin, boscalid, chlorpropham, cyprodinil, difenoconazole, fenhexamid, iprodione, tebuconazole, and lamda-cyhalothrin), was associated with a higher BW loss in men (β(95 %CI) = -0.05 (-0.08; −0.03) kg/year, p < 0.0001). No associations were observed for NMF1 and 4. This study suggests a role of pesticide exposure, inferred from dietary patterns, on BW change, with sexually dimorphic actions, including a potential role of a lower exposure to synthetic pesticides on BW change in women. In men, exposure to a specific pesticide mixture was associated with higher BW loss. The underlying mechanisms need further elucidation.