Polyhydroxyalkanoates (PHAs) are natural polymers produced under specific conditions by certain organisms, primarily bacteria, as a source of energy. These up-and-coming bioplastics are an undeniable asset in enhancing the effectiveness of drug delivery systems, which demand characteristics like non-immunogenicity, a sustained and controlled drug release, targeted delivery, as well as a high drug loading capacity. Given their biocompatibility, biodegradability, modifiability, and compatibility with hydrophobic drugs, PHAs often provide a superior alternative to free drug therapy or treatments using other polymeric nanocarriers. The many formulation methods of existing PHA nanocarriers, such as emulsion solvent evaporation, nanoprecipitation, dialysis, and in situ polymerization, are explained in this review. Due to their flexibility that allows for a vessel tailormade to its intended application, PHA nanocarriers have found their place in diverse therapy options like anticancer and anti-infective treatments, which are among the applications of PHA nanocarriers discussed in this article. Despite their many positive attributes, the advancement of PHA nanocarriers to clinical trials of drug delivery applications has been stunted due to the polymers' natural hydrophobicity, controversial production materials, and high production costs, among others. These challenges are explored in this review, alongside their existing solutions and alternatives.