In the last century, conventional antibiotics have played a significant role in global healthcare. Antibiotics support the body in controlling bacterial infection and simultaneously increase the tendency of drug resistance. Consequently, there is a severe concern regarding the regression of the antibiotic era. Despite the use of antibiotics, host defence systems are vital in fighting infectious diseases. In fact, the expression of ribosomal antimicrobial peptides (AMPs) has been crucial in the evolution of innate host defences and has been irreplaceable to date. Therefore, this valuable source is considered to have great potential in tackling the antimicrobial resistance (AMR) crisis. Furthermore, the possibility of bacterial resistance to AMPs has been intensively investigated. Here, we summarize all aspects related to the multiple applications of ribosomal AMPs and their derivatives in combating AMR.