Polyelectrolyte complexes (PICs) have emerged as promising candidates in the field of drug delivery.This manuscript presents a comprehensive investigation organized into four main sections to elucidate the potential of PICs for drug delivery applications.The first section provides a foundational understanding of polyelectrolytes, highlighting their unique properties and characteristics.Subsequently, we delve into an examination of the physicochemical properties of polyelectrolytes, shedding light on the mechanisms governing the formation of PICs and the critical parameters involved in preparing polyelectrolyte nanoparticles.In the third section, we explore the formation of polyelectrolyte-based nanoparticles, encompassing hydrophilic polyelectrolytes, hydrophobically modified polyelectrolytes, and PICs formed with oppositely charged polymers.This section offers insights into the versatile applications of PICs in drug delivery systems.The final section delves into the biological functions of polyelectrolytes, revealing their role in enhancing cellular uptake, facilitating endosomal escape, acting as immune stimulators, and exhibiting antitumor activity.These insights emphasize the potential of PICs to overcome barriers in drug delivery and enhance therapeutic outcomes.In summary, this manuscript serves as a comprehensive resource for researchers and practitioners in the field, offering a holistic understanding of the multifaceted applications of PICs in drug delivery.