Polyhydroxyalkanoates (PHAs) are polymers synthesized by diverse bacteria for carbon and energy storage applications. PHAs are biodegradable and nontoxic. They also exhibit properties similar to those of petroleum-based polymers. Therefore, these materials are promising alternatives to conventional plastics. This review aims to provide a comprehensive overview of PHA research, from production to application. This review summarizes the thermal and mechanical properties of various PHA homopolymers and copolymers, and compares them with those of common petroleum-based polymers. This comparison indicates that elongation at break is a major weakness of many PHAs. Different organic wastes used in PHA microbial production by mixed culture fermentation are summarized in this review. Important parameters of feedstock fermentation, culture selection, and PHA accumulation were compared. The pH and organic loading rate significantly affected the overall PHA yield, and various feedstocks led to different PHA compositions. Physical (blending and fiber reinforcement) and biological (cofeeding) modifications to improve the mechanical properties of PHA are elaborated in this review. Tensile properties are the major improvements among the mechanical properties after modification. Current applications of PHA and its derivatives are also presented in this work. They are primarily applied in the medicine, agriculture, and packaging industries. The widespread application of PHA faces challenges such as high production costs and limited mechanical properties. This study intends to stimulate further research into cost-effective methods for PHA production and to explore additional modification techniques.