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Background Food-related illnesses have become more prevalent globally over time, having a detrimental impact on the health and economic prosperity of both emerging and developed nations. A large percentage of these diseases are caused by food-borne infections, both globally and locally. Objective To determine food safety and hygiene practices of food vendors in the Bibiani Municipality. Method A descriptive cross-sectional design was employed in this study. A quota sampling technique was used to select 152 food vendors from Bibiani. The community was divided into three parts: Bibiani, Anwhiaso, and Bekwai. The data collection tool was structured questionnaires and exported into Statistics and Data 15.0 (STATA 15.0). The data were analyzed descriptively and presented as frequency counts, simple percentages, and tables. Results Out of 152 respondents, 89.5% put leftover foods in the refrigerator for preservation, 4.6% put food pans in water, 76.3% used a serving spoon when dishing food, 5.3% used bear hands, 64.5% used soap and water during hand washing, and 73.0% had done a medical examination; 82.2% wore aprons as well as hair covers during the cooking and serving of food. Conclusion The majority of respondents had satisfactory safety and hygiene practices, while some still had several unsafe hygienic practices. Recommendation The government of Ghana and MMDAs should establish the pre-requisite standard operating procedures for all institutions undertaking hospitality regarding food safety and hygiene.