Antibiotics produced by soil microorganisms have been widespread and have cured the most prevalent diseases since 1940s. However, recent bacterial resistance to existing antibacterial drugs is causing a public health crisis. The structure–activity relationship of antibiotics needs to be established to search for existing antibiotics-based next-generation drug candidates that can conquer the challenge of bacterial resistance preparedness, which relies on the development of highly efficient total synthesis strategies. The solid-phase strategy has become important to circumvent tedious intermediate isolation and purification procedures with simple filtrations. This review will give a brief overview of recent applications of solid-phase strategy in the total synthesis of antibiotics.