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A lethal pandemic has impacted the global community. Concurrently, the world is witnessing significant climate changes. The ongoing environmental alterations are contributing to viral and bacterial infections, increasing the consumption of antibiotics. The use of antibiotics has risen markedly during the COVID-19 pandemic and continues into the post-COVID era. Broadspectrum antibiotics, which target a wide array of disease-causing bacteria, are the most commonly prescribed medications. There has been a notable increase in the accessibility and affordability of antibiotics among the general population. A primary factor contributing to this trend is the over-the-counter availability of antibiotics, which is compounded by their frequent use. The rural and urban populations exhibit varying levels of access to and affordability of quality healthcare. This divergence in lifestyle also affects the gut microbiome. Patients often complete only a portion of their prescribed antibiotic course. Such habitual use of antibiotics, coupled with the failure to complete the prescribed regimen, poses a significant and potentially irreversible threat to the healthy microbiome of the human intestine, leading to a concerning pattern of antibiotic resistance. This study examines the antibiotic resistance patterns in the post-COVID context, specifically regarding the gut microbiomes of rural and urban populations in West Bengal, underscoring the urgent need for responsible antibiotic use.