This study aimed to investigate the effect of pumpkin (Cucurbita maxima) seed supplementation on the anthropometric measurements, biochemical parameters, and blood pressure (BP) of Indian women with metabolic syndrome (MetS). Initially, in vitro antioxidant activities of pumpkin seeds extract were assessed using standard methods. In vitro alpha-amylase, alpha-glucosidase, and dipeptidyl peptidase IV (DPP-IV) inhibition effects, along with glucose uptake assay using 3T3-L1 cell lines were performed to determine the antidiabetic effects of the seeds extract. Fatty acids and phytoconstituents were identified using gas chromatography-mass spectrometry (GC–MS). Indian women aged 30–50 years, having MetS were assigned either to intervention (n = 21) or control (n = 21) group on a random basis. Participants in the intervention group received 5 g of pumpkin seeds for 60 days. Participants in both intervention and control were advised to follow certain dietary guidelines throughout the study. Pumpkin seeds extract exhibited not only strong reducing power but also scavenged DPPH and ABTS^●+ free radicals with low IC₅₀ values. Pumpkin seeds inhibited alpha-amylase, alpha-glucosidase, and DPP-IV enzymes at varying concentrations with IC₅₀ values of 138, 22, and 246 µg/mL, respectively. Furthermore, glucose uptake was enhanced by 213% at 300 ng/mL on the 3T3-L1 cell line. GC–MS analysis showed the presence of propyl piperidine, flavone, oleic acid, and methyl esters of fatty acids in the seed extract. On comparing the changes in mean reduction/ increment in the anthropometric measurements as well as biochemical parameters and BP between the groups, significant difference (P = 0.012) was observed only for fasting plasma glucose. Findings of the present study highlight the role of pumpkin seeds as a cost-effective adjunct in treating MetS.