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The present study aimed to determine the effects of biostimulants on the physicochemical parameters of the agricultural soil of quinoa under two water regimes and to understand the mode of action of the biostimulants on quinoa for drought adaptation. We investigated the impact of two doses of vermicompost (5 and 10 t/ha) and arbuscular mycorrhizal fungi applied individually, or in joint application, on attenuating the negative impacts of water shortage and improving the agro-physiological and biochemical traits of quinoa, as well as soil fertility, under two water regimes (well-watered and drought stress) in open field conditions. Exposure to drought decreased biomass, leaf water potential, and stomatal conductance, and increased malondialdehyde and hydrogen peroxide content. Mycorrhiza and/or vermicompost promoted plant growth by activating photosynthesis machinery and nutrient assimilation, leading to increased total soluble sugars, proteins, and antioxidant enzyme activities in the leaf and root. After the experiment, the soil’s total organic matter, phosphorus, nitrogen, calcium, and soil glomalin content improved by the single or combined application of mycorrhiza and vermicompost. This knowledge suggests that the combination of mycorrhiza and vermicompost regulates the physiological and biochemical processes employed by quinoa in coping with drought and improves the understanding of soil–plant interaction.