Abstract: Terpenoid indole (TIAs) and β-carboline alkaloids (BCAs), such as suppressant reserpine, vasodilatory yohimbine, and antimalarial quinine, are natural compounds derived from strictosidine. These compounds can exert powerful pharmacological effects but be obtained from limited source in nature. the whole biosynthetic pathway of TIAs and BCAs, The Pictet–Spengler reaction catalyzed by strictosidine synthase (STR; EC: 4.3.3.2) is the rate-limiting step. Therefore, it is necessary to investigate their biosynthesis pathways, especially the role of STR, and related findings will support the biosynthetic generation of natural and unnatural compounds. This review summarizes the latest studies concerning the function of STR in TIA and BCA biosynthesis, and illustrates the compounds derived from strictosidine. The substrate specificity of STR based on its structure is also summarized. Proteins that contain six-bladed four-stranded β-propeller folds in many organisms, other than plants, are listed. The presence of these folds may lead to similar functions among organisms. The expression of STR gene can greatly influence the production of many compounds. STR is mainly applied to product various valuable drugs in plant cell suspension culture and biosynthesis in other carriers.