Antimicrobial resistance is a developing worldwide health concern that calls into question the effectiveness of traditional medicines. In the past few decades, more research has concentrated on alternate approaches, including the use of chemicals originating from plants and novel principles and its nanoparticles to combat AMR. Bioactive compounds, like flavonoids, terpenoids, polyphenols, and many more, possess intrinsic antibacterial, anti-virulence, and immunomodulatory characteristics that disrupt bacterial communication, biofilm formation, and ultimately diminish their pathogenicity in the host. Moreover, recent studies indicate that certain peptides derived from plants may function as quorum sensing receptor antagonists (QSRA), interfering with bacterial quorum sensing regulatory pathways and diminishing the synthesis of virulence factors and resistance mechanisms. Concurrent advancements in nanotechnology have yielded nanoparticles with distinct physicochemical properties, such as titanium dioxide, gold, silver, and zinc oxide, which enhance penetration through microbial barriers, facilitate targeted drug delivery, and induce reactive oxygen species (ROS) that result in cellular damage. This dual approach exploits the synergistic potential of both entities: nanoparticles, which are a powerful antimicrobial agent and also efficient carriers that improve the bioavailability and effectiveness of plant-derived compounds, while phytochemicals and plant peptides offer a natural source of structurally diverse antimicrobial agents with lower toxicity and a reduced risk of resistance development. QSAR methods also play a crucial role in predicting the target pathway for effective antimicrobial agents too.