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The World Health Organization (WHO) states that in developing nations, there are three million cases of agrochemical poisoning. The prolonged intensive and indiscriminate use of agrochemicals adversely affected the soil biodiversity, agricultural sustainability, and food safety, bringing in long-term harmful effects on nutritional security, human and animal health. Most of the agrochemicals negatively affect soil microbial functions and biochemical processes. The alteration in diversity and composition of the beneficial microbial community can be unfavorable to plant growth and development either by reducing nutrient availability or by increasing disease incidence. Currently, there is a need for qualitative, innovative, and demand-driven research in soil science, especially in developing countries for facilitating of high-quality eco-friendly research by creating a conducive and trustworthy work atmosphere, thereby rewarding productivity and merits. Hence, we reviewed (1) the impact of various agrochemicals on the soil microbial diversity and environment; (2) the importance of smallholder farmers for sustainable crop protection and enhancement solutions, and (3) management strategies that serve the scientific community, policymakers, and land managers in integrating soil enhancement and sustainability practices in smallholder farming households. The current review provides an improved understanding of agricultural soil management for food and nutritional security.