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Antibiotic resistance is a major risk to human health worldwide due to antibiotic- and multidrug-resistant bacteria, especially in the case of serious infections, which limits the availability of antimicrobial treatment options. Focusing on the bacterial resistance mechanisms against antibiotics and the conventional strategies used to combat antimicrobial resistance, this review highlights the history of antibiotics and their target mechanisms, mentions the strategy limitations, provides the most recent novel alternative therapies to combat resistance, and illustrates their mode of action and applications that may treat several infectious diseases caused by bacterial resistance. Finally, this paper mentions future prospects that we believe would make a considerable difference in the microbial resistance battle. Novel antibiotic alternative therapies, including nanomaterial therapy, antimicrobial photodynamic therapy, hybrid antimicrobial therapy, and phage therapy, are covered in this review.