Defatted Lagenaria siceraria seeds and those of Cucumeropsis mannii, obtained after lipid extraction using food-grade hexane, were converted into flours (defatted Lagenaria siceraria seeds flours, LSDSF; defatted Cucumeropsis mannii seed flours, CMDSF), and analysed for their chemical and amino acid (AA) compositions, protein fractions, protein molecular weight distribution, granular surface morphology by scanning electron microscopy, and thermal properties by differential scanning calorimetry. In addition, their antioxidant activities were evaluated using DPPH radical scavenging and phosphomolybdate reducing power assays. LSDSF and CMDSF contained mainly globular shaped proteins with high thermal stability. Composition wise, these proteins primarily consisted of globulins, glutelins, and albumin. AA analysis of the total protein identified 18 amino acids including all the essential AA. These flours thus could be potential sources of antioxidant compounds with higher activity in aqueous than in methanolic extract. Based on their composition and physicochemical characteristics, LSDSF and CMDSF are potentially good ingredients usable in food systems with low lipid oxidation.