Background: Food insecurity has involved more than 750 million individuals worldwide. The association of food insecurity with socio-economic factors is also undeniable demand more consideration. Food insecurity will become a global priority by 2030. This systematic review and meta-analysis examined current literature concerning the association between food insecurity and psychological distress. Methods: Relevant researches were identified by searching databases including PubMed, EMBASE, Scopus, and Web of Science, ProQuest, and Cochrane Library up to June 2024 without language limitation. Then a snowball search was conducted in the eligible studies. The quality assessment was made through Newcastle-Ottawa Scale. Results: Data were available from 44 cross-sectional articles for systematic review and 17 eligible articles for meta-analysis with 2,267,012 and 1,953,636 participants, respectively. Findings support the growing segment of literature on the association between food insecurity and psychological distress. The highly represented groups were households with low income. Psychological and diabetic distress was directly associated with food insecurity as it increased the odds of distress to 329% (OR: 3.29; 95% CI: 2.46-4.40). Sleep problems, anxiety, depression, lower life satisfaction, obesity, and a higher rate of smoking were among the secondary outcomes. Conclusion: Food insecurity was a common stressor that can have a negative impact on psychological well-being and even physical health. The findings should be considered in the public health and making policy-making process.