Background: Nowadays, more than 1 billion people suffer from food insecurity worldwide. Food insecurity is recognized as an important determinant of health, and both food insecurity and diseases are public health concerns. This study aimed at determining the association between food insecurity and self-reported history of infectious and parasitic diseases among household mothers in Zahedan, southeast of Iran. Methods: This cross-sectional study was conducted on 2160 households in Zahedan. Food insecurity of the households was assessed through USDA 18-item questionnaire. Demographic data and questions about history of infectious and parasitic diseases in mothers were collected through interviewing the mothers. The data were analyzed using chi-square test and logistic regression model. Results: Of the household mothers, 58.8% experienced food insecurity, 11.5% reported history of infectious diseases, and 1.1% experienced parasitic diseases in the last 3 months. After adjusting for the selected variables, a positive association was detected between food insecurity and history of infectious (OR, 2.29; 95% CI, 1.66 -3.18) and parasitic diseases (OR, 3.86; 95% CI, 1.07 -13.93) in mothers. Conclusions: Food security seems a controllable environmental factor that may cause some positive results in the fight against diseases. On the other hand, preventing and controlling infectious and parasitic diseases may in turn result in reduction of food insecurity.