It is increasingly evident that oxidative stress and the presence of free radicals are a major cause of many disease processes that may aggravate the disease course, or create new effects that could cause further alterations in patient's health or impair their quality of life. The purpose of this study was to determine the antioxidant activity of extracts from seeds of four varieties of Cucurbita spp: (Hybrid between C. moschata and C. maxima Duchesne ex Lam) Tetsukabuto, C. mixta Pangalo (calabaza rayada), C. moschata (Duchesne ex Lam.) Duchesne ex Poir. (coreanito) and C. maxima Duchesne (calabaza plomo), in relation to their content of total phenols and flavonoids. Extracts of decreasing polarity were obtained using the following solvents: acidified water, methanol, acetone and ethyl acetate, the total phenols and flavonoids were quantified by the FolinCiocalteau and complexation with AlCl3 to 5% respectively. To determine the antioxidant activity of extracts bleaching technique free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) was used. The total phenolic content was to Tetsukabuto (165.48 ± 0.94), calabaza rayada (275.10 ± 6.86), coreanito (118.79 ± 3.72) calabaza plomo (212.87 ± 7 51) (mol GAE/g of sample). Flavonoids values ranged from (32.03 ± 1.39) and (96.63 ± 1.14) (quercetin mg/g sample). The antioxidant activity expressed as median inhibitory concentration (IC50) showed the following results: Tetsukabuto (117.69 ± 5.81) calabaza rayada (77.75 ± 3.64); coreanito (110.67 ± 1.70), calabaza plomo (87.39 ± 8.64) (mg/ml). A one-way analysis of variance showed significant differences (p < 0.05) among the varieties studied. The results obtained show a clear relationship between the content of total phenolics and flavonoids with antioxidant activity, with C. mixta Pangalo variety showed higher antioxidant activity and can be considered a source of natural antioxidants to produce a beneficial effect on health.