Ruspolia differens Serville (Orthoptera: Tettigonidae) is a highly nutritious and luxurious insect delicacy that is consumed as a food source in many African countries. However, the nutrient profile of R. differens in different geographical regions have received limited research interest. Here, we provide comprehensive evidence of geographical impact on the nutrient profile of R. differens and its potential to meet the recommended dietary intake of the population. Our results demonstrated that proximate composition, fatty acids, amino acids, minerals, vitamins, and flavonoid contents of R. differens collected from five districts in Uganda varied considerably. The crude protein (28–45%), crude fat (41–54%), and energy (582–644 Kj/100 g) contents of R. differens exceed that reported from animal origins. The highest crude protein, crude fat, and carbohydrate contents of R. differens were recorded in Kabale, Masaka, and Kampala, respectively. A total of 37 fatty acids were identified with linoleic acid (omega-6 fatty acid) being the most abundant polyunsaturated fatty acid in R. differens from Kabale, Masaka, and Mbarara. All essential amino acids were recorded in R. differens, particularly histidine with values exceeding the daily requirement for adults. Mineral and vitamin content differed significantly across the five districts. The highest quantity of flavonoids was recorded in R. differens from Hoima (484 mg/100 g). Our findings revealed that R. differens could be considered as functional food ingredients capable of supplying essential macro- and micronutrients that are critical in curbing the rising food insecurity and malnutrition in the regions.