The use of bio-stimulants (BSs) has become an important policy in managing many stressed crop plants through the regulation of the balance of phytohormones, osmo-protectors (OPs), antioxidant systems, and gene expression, all of which reflect plant growth and productivity. Garlic + onion extract (GOE) at a concentration of 2.0–3.0% and diluted bee honey solution (BHs) at a concentration of 1.0–1.5% were applied exogenously to squash (Cucurbita pepo) plants subjected to cadmium (Cd) + lead (Pb) stress (0.3 mM CdCl2 + 0.3 mM PbCl2). The objective was to determine the effects of these treatments on growth characteristics, organic metabolites/biomolecules, and mineral nutrients. Cd + Pb stress significantly increased electrolyte leakage (EL, 103%) and malondialdehyde (MDA, 90%) because of an increase in hydrogen peroxide (H2O2, 145%) and superoxide (O2•−, 152%) levels, and contents of abscisic acid (ABA, 164%), Cd (674–711%), and Pb (754–805%). Consequently, marked increases in the contents of OPs and non-enzymatic antioxidants (28–133%), activities of antioxidant enzymes (48–80%), and expressions of enzyme genes (60–84%) were observed. The administration of Cd + Pb treatment reduced plant growth and development parameters (25–59%), yield components (61–86%), photosynthetic components (27–67%), leaf proportional water content (26%), indole-3-acetic acid (IAA, 44%), gibberellic acid (GA3, 56%), and cyto-kinin (CKs, 49%) contents. Nonetheless, the administration of GOE, BHs, and GOE + BHs attenuated the adverse impacts of Cd + Pb stress. The best treatment was GOE + BHs which significantly decreased EL (52%) and MDA (49%) because of a reduction of O2•– (61%), H2O2 (60%), ABA (63%), Cd (89–91%), and Pb (89–91%) levels. This positive outcome was linked to an increase in the OPs’ (22–46%) and non-enzymatic antioxidant (27–46%) levels, activities of enzymes (26–44%), and enzyme gene expressions (35–40%), all of which contributed to the promoted relative water content (RWC, 37%), pigment contents (47–194%), hormonal levels (82–132%), growth traits (31–149%), yield components (154–626%), and fruit quality traits (31–92%). From these results, it can be concluded that treatment of GOE + BHs is recommended as a foliar application to reduce the adverse effects of Cd + Pb stress treatment in squash.