Food is a basic human need important for the survival of all human beings. The rapidly growing world population puts pressure on food sources, inviting the need to devise mechanisms to sustain it. Biotechnology has developed important measures for improving plants and livestock as a remedy for food security with aim to achieve the Sustainable Development goal two (2). Globally, the adoption and use of genetically modified foods (GMFs) has been controversial as it is in Uganda today due to concerns related to the risk uncertainties. This study was therefore conducted to assess the public perceptions, knowledge and factors that influence the acceptability of genetically modified foods in Kampala City. This was a cross sectional quantitative study that involved one hundred and ninety-eight participants. The data were collected using a survey tool and summarized using descriptive and linear regression analysis. The findings of this study showed that almost two-thirds of participants (129/198, 65%) had some basic knowledge on genetically modified foods. About 45.3% (90/198) of the participants perceived genetically modified foods as being unsafe for human consumption. Eighty-eight participants (44.3%) perceived them as being associated with major human health and environmental safety concerns. The acceptability of these foods was significantly associated with gender, education level, nutritional value and health effects. Female participants were more likely to accept genetically modified foods (OR.4.84 95% CI: 1.37 - 7.68). Those who perceived genetically modified foods as being of high nutrition value were more likely to accept them (OR. 3.07, 95% CI: 1.27 - 7.37). The public is predominantly aware of genetical modified foods since a big proportion had basic knowledge about them although with a lot of misinformation. People with a higher education level had positive perceptions on the use of these foods hence a need to educate the public to dispel misinformation that influences their acceptability.