Natural products with high oxidation states and complex chemical skeletons exhibit diverse bioactivities due to their unique interactions with biological targets. The high oxidation state is characterized by the presence of multiple oxygen-containing functional groups such as hydroxyl groups, carbonyl groups, and epoxides that are usually tough to construct selectively. In recent years, thanks to the development of efficient strategies and sophisticated methodologies, significant advancements have been made in the total syntheses of highly oxidized natural products (HONPs), which are reviewed herein.