Large-scale sustainable agriculture presents a formidable challenge globally, resulting in severe food insecurity for approximately 52% and 48% of people living in rural and urban areas, respectively. An estimated 690 million individuals suffer from hunger annually due to the high cost of chemical fertilizers and other factors. To reduce costs, source-separated urine offers a promising alternative for crop production, despite containing more nitrogen and phosphorus than traditional fertilizers. However, human urine also contains pharmaceuticals and micropollutants with adverse effects on human health and the environment. Human urine provides essential micronutrients for plant growth, with studies showing similar nutrient concentrations between concentrated urine and mineral fertilizers. Nevertheless, the presence of heavy metals and other contaminants in urine raises safety concerns. While urine diversion toilets can safely collect urine, their use as a liquid fertilizer requires careful consideration due to the presence of disease-causing organisms, pharmaceuticals, and metabolites that contribute to water and soil contamination. Consumers and farmers alike worry about the safety of crops fertilized with urine, given the perception of disease-causing pathogens. This review explores the impact of urine and chemical fertilizers on plant yield as well as the effects of heavy metals, pharmaceuticals, and microplastics on human health and the environment. Various methods to remove antibiotics from urine, such as membrane bioreactors combined with complex chemicals and physicochemical processes, were also examined. These methods, including activated powdered carbon, nano-filtration, ozone, and ozone/UV, target specific antibiotics and their metabolites to ensure the safety of urine-derived fertilizers.