In the primitive era, humans benefited partially from plants and metals to treat microbial infections. Later these infections were cured with antibiotics but further suffered from resistance issues. In searching of an alternative, researchers developed an adjuvant therapy but were hampered by spreading resistance. Subsequently, nanoparticles (NPs) were proposed to cease the multi-drug resistant bacteria but were hindered due to toxicity issues. Recently, a novel adjuvant therapy employed metals and botanicals into innovative nanotechnology as nano-antibiotics. The combination of green synthesized metallic NPs with antibiotics seems to be a viable platform to combat against MDR bacteria by alleviating resistance and toxicity. This review focuses on the primitive to present era dealings with bacterial resistance mechanisms, newer innovations of nanotechnology and their multiple mechanisms to combat resistance. In addition, special focus is paid on greener NPs as antibiotic carriers, and their future prospects of controlled release and toxicity study.