Severe drought stress affects the production of vegetable-type soybean (Glycine max L. Merrill), which is in infancy for Africa despite its huge nutritional benefits. This study was conducted under controlled environmental conditions to establish the effects of severe drought stress on ascorbate peroxidase (APX), guaiacol peroxidase (GPX), and glutathione reductase (GR) activities as well as proline, total soluble sugars (TSS), and hydrogen peroxide (H2O2) contents of five vegetable-type soybean cultivars (UVE8, UVE14, UVE17, AGS354, AGS429) at flowering and pod-filling stages. Drought induced significant increases in the contents of proline (selectively at pod filling for AGS429), TSS (at both stages for AGS429, and only at pod filling for UVE14), and malondialdehyde (AGS354 at flowering; UVE17 at pod filling). UVE8 and AGS354 had the highest H2O2 levels at flowering under drought stress, while AGS429 had the lowest. However, AGS429 was the only cultivar with significantly increased H2O2 under drought stress. Furthermore, drought stress induced significant increases in APX, GPX, and GR activities at flowering for AGS429. AGS354 recorded the highest decline for all antioxidative enzymes, while UVE17 decreased for GPX only. All biochemical parameters, except H2O2, were significantly higher at pod filling than at the flowering stage. The relationship between H2O2 and total seed mass (TSMP) or total seed per plant (TSP) was significantly positive for both stages, while that of TSS (at flowering) and proline (at pod filling) were significantly related to total pods per plant (TPP). The study suggests that during drought, the tolerance responses of vegetable-type soybean, APX, GPX, and GR (especially at the flowering stage), function in concert to minimize H2O2 production and lipid peroxidation, thereby allowing H2O2 to function in the signaling events leading to the induction of drought tolerance. The induction of TSS at flowering and proline at pod filling is important in the drought tolerance response of this crop.