Drugs, which are known as antibiotics, treat bacterial infections in both humans and animals. Needless to say, a vast array of microorganisms, including fungi and bacteria, develop antibiotics. Contaminations brought on by drug-resistant bacteria have become a significant problem for public healthcare systems in recent years. In actuality, the introduction of antibiotics has contributed to the rise of bacteria resistant to multiple drugs. In this review, we have tried to analyze detailed aspects of the antimicrobial resistance (AMR) mechanism conferred by both gram-negative and gram-positive bacteria by taking ESKAPE, i.e., E. coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, Enterobacter spp. etc. respectively. Herein, we discussed novel redesigning methods for conventional antibiotics and provided a viewpoint on the subject. There is an acute need to discover and utilize unconventional methods for antibacterial drug development to block and tackle these global threats. It is essential to reduce the excessive use of antibiotics and reduce the possibility of unknown MDR bacteria. Furthermore, it is important to discover new classes of modified antibiotics to enhance their lifespan and deal with MDR bacteria.