The escalating global water scarcity and increasing food demand have accelerated the use of reclaimed water for agricultural irrigation, particularly in arid and semi-arid regions. However, the pervasive presence of antibiotic residues in reclaimed water, originating from incomplete wastewater treatment and continuous environmental input, poses significant risks to crop health, soil ecosystems, and food safety. Antibiotics such as fluoroquinolones, sulfonamides, and tetracyclines, detected at ng/L to mu g/L levels in reclaimed water, accumulate in crops, disrupt physiological processes, and promote antibiotic resistance genes. This comprehensive review critically analyzed the accumulation patterns, and mitigation strategies of antibiotics in crops under reclaimed water irrigation. The accumulation pattern is governed by a complex interplay of factors, including the physicochemical properties of antibiotics and soil, the presence of co-pollutants, crop species and their associated microbiomes, environmental conditions, and irrigation management practices. By integrating insights from molecular biology, environmental science, and agriculture, the review highlighted innovative approaches like metabolic reprogramming, phytoremediation, and synthetic microbial communities to enhance crop resilience and reduce antibiotic uptake. Furthermore, it identified research gaps and future directions, emphasizing the need for a "One Health" perspective to safeguard agricultural sustainability and human health.