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Abstract Antibiotic resistance genes (ARGs) are considered a contaminant of emerging concern in the environment. ARGs are widely distributed in the environment (e.g., soil, biosolids, plants, wastewater), companion and food-producing animals, wildlife, and insects. Soils are important reservoirs of ARGs and constitute a major pathway for the exchange of ARGs among microorganisms, including clinically relevant pathogens. Naturally available clays and clay minerals show high affinity to ARGs and antibiotics, which can be exploited to develop methods for mitigating ARGs contamination in soil, biosolids, and water. The mechanism of ARGs retention, degradation, and transformation on natural and modified clay surfaces is complex and requires further understanding to develop scalable remediation methods. Here, we discuss the source, availability, and distribution of antibiotics and ARGs in wastewater and soil, and their interactions with natural and modified clays and clay minerals to seek effective strategies for mitigating the overlooked pandemic of antimicrobial resistance (AMR). We shed light on future research requirements to extend the use of inexpensive clay adsorbents and develop nature-based solutions using these materials for mitigating AMR in the environment.