Chemicals are comprehensively used worldwide to control herbs, weeds, pests, and other competing agents with various growing crops. The consumption of crops grown with these chemicals (even in small quantities) can upshot into accumulation in the human body. People can accidentally inhale these hazardous chemicals if they are in an area where they were applied. These chemicals can be ingested in a human with contaminated food and drinks. Ultimately it causes various adverse effects (chronic toxicity, teratogenic, mutagenic, carcinogenic effect, reproductive, and organ toxicity) on human health. Among the pool of these chemicals used as pesticides in the environment, exposure of endosulfan to humans has a potential health risk throughout the globe. The poisoning of endosulfan is reported frequently in society, therefore, this article highlights the toxicological and other harmful properties of endosulfan to humans and emphasized its essential biomonitoring. Its quick monitoring and effective hazard evaluation are possible with multiomics technologies and some other analytical approaches. This review summarizes the introduction and mechanism of action of endosulfan along with some other toxic chemicals used in the agriculture work, the toxicity of endosulfan in human/environment, and importantly its biomonitoring (detection of chemicals and their metabolites in a biological sample) in human because biomonitoring is often considered as the most preferred method. Biomonitoring could be easily done in human samples (blood, hair, milk, and urine) with a multi-omics approach, which is a quick, reliable, and state-of-the-art technique.