Drought stress threatens many regions of the world, resulting in reduced productivity for many vegetable crops, as it negatively affects higher plants, as it causes an increase in the production of free radicals, which are responsible for the oxidation and destruction of plant cells. So, this research work was carried out using squash as tested plant, aiming to unravel the multifaceted interplay among irrigation treatments at various levels (100, 75 and 50 % of irrigation requirement IR), organic fertilizer at different rates (0.0, 12 and 24 m3 ha-1) and various stress-alleviating substances (chitosan, yeast and polyethene glycol PEG). Plant height, fresh and dry weights, leaves area, chlorophyll a and b were measured at 45 days from sowing as well as fruit yield of all pickings was measured as total yield. The squash plants receiving 100% of IR demonstrated the highest values for all aforementioned traits. Conversely, these values exhibited a gradual decrease with reduced irrigation levels, reaching their lowest values in the treatment with 50% of IR. For example, the highest values of dry weight (130.41 g plant-1 for 1st season) were recorded with 100% of IR, while the lowest values (120.24 g plant-1 for 1st season) were recorded with 50% of IR. Furthermore, there are a progressive increase in the values as the application rate of organic fertilizer increased from 0.0 to 12 and subsequently to 24 m3 ha-1.  Spraying stimulants exerted a notable impact with the most effective treatment being PEG followed by yeast then chitosan. Notably, the performance in terms of the oxidative stress indicators and enzymatic antioxidants, subjected to water deficit (75% of IR) and fertilized with organic fertilizer (24 m3 ha-1), combined with stimulant sprays, surpassed those under conventional irrigation (100% of IR) in the absence of organic fertilizer. Finally, these findings align with the sustainable development goals, such as SDG2 (Zero Hunger) and SDG12 (Responsible Consumption and Production). Finally, these findings align with the Sustainable Development Goals, such as SDG2 (Zero Hunger) and SDG12 (Responsible Consumption and Production) via the potential of holistic strategies to mitigate the adverse effects of water scarcity on vegetable crops.