Soils contaminated with radionuclides pose a long-term radiation hazard to human health through food chain exposure and other pathways. The uptake, accumulation, and distribution of ¹³³Cs, individual ⁸⁸Sr, and combined ⁸⁸Sr + ¹³³Cs, with their physiological and biochemical responses in greenhouse-potted soil-based cucumber (Cucumis sativus L.), were studied. The results from the present study revealed that the uptake, accumulation, TF, and BCF ability of cucumber for ⁸⁸Sr + ¹³³Cs were greater than for ¹³³Cs and ⁸⁸Sr while the concentration was the same in the soil (10, 20, 40, 80, and 160 mg kg⁻¹). The highest ⁸⁸Sr + ¹³³Cs accumulation was 2128.5 µg g⁻¹dw, and the highest accumulation values of ¹³³Cs and ⁸⁸Sr were 1738.4 µg g⁻¹dw and 1818.2 µg g⁻¹dw (in 160 mg kg⁻¹), respectively. The lowest ⁸⁸Sr + ¹³³Cs, ¹³³Cs, and ⁸⁸Sr accumulation values were 416.37 µg g⁻¹dw, 268.90 µg g⁻¹dw, and 354.28 µg g⁻¹dw (10 mg kg⁻¹), respectively. MDA content was higher under ⁸⁸Sr and ¹³³Cs stress than under ⁸⁸Sr + ¹³³Cs stress. Chlorophyll content increased at 10 and 20 mg kg⁻¹; however, it decreased with increasing concentrations (40, 80, and 160 mg kg⁻¹). Proline content and the activities of CAT, POD, and SOD were lower under ¹³³Cs and ⁸⁸Sr than ⁸⁸Sr + ¹³³Cs stress. The ⁸⁸Sr, ¹³³Cs, and ⁸⁸Sr + ¹³³Cs treatment concentrations sequentially induced some enzymes over 60 days of exposure, suggesting that this complex of antioxidant enzymes—CAT, POD, and SOD—works in combination to reduce the impact of toxicity of ⁸⁸Sr, ¹³³Cs, and ⁸⁸Sr + ¹³³Cs, especially in young leaves. It is concluded that cucumber reveals considerable phytoremediation capabilities due to unique growth potential in contaminated substrate and is suitable for the bioreclamation of degraded soils. The plant is especially applicable for efficient phytoextraction of ⁸⁸Sr + ¹³³Cs contamination.