Policymakers and development organizations have widely identified homegardening as an activity that can alleviate global pressure on food production and food security in developing countries. In Sub-Saharan Africa, studies on homegardens have examined species diversity and conservation, as well as factors influencing species composition and landscape management. However, little attention has been given to understanding the relationship between food security and commercialization. Therefore, this study examines for the role of commercialization of homegardens and its potential to contribute to food security in northern areas of Ghana. A mixed sampling technique was employed to identify and interview 120 homegardeners. Probit regression analysis revealed that homegarden size, ownership status, and water availability, together with farmer’s age and gender, were statistically significant factors influencing market orientation. Propensity score matching and endogenous treatment regression showed that a higher degree of market orientation of homegarden produce significantly contributes to the food security of farmers. Gender, educational status, and access to input subsidies influenced the food security situation of the homegardeners. Our findings suggest that government and development agencies should promote and support homegardens as a promising farming practice that enhances rural development, food security and overall livelihood resilience in Sahel region, such as northern Ghana.