Indoles, pivotal to the realm of drug discovery, underpin numerous FDA-approved therapeutics. Despite their clinical benefits, pharmacokinetic and toxicity concerns have occasionally hampered their broader application. A notable advancement in this domain is the substitution of hydrogen atoms with deuterium, known as deuterium modification, which significantly enhances the pharmacological properties of these compounds. This review elucidates the progression of deuterium chemistry, culminating in approval of Deutetrabenazine in 2017. This milestone has catalyzed additional research into deuterated indoles, such as Dosimertinib, which have demonstrated enhancements in stability, toxicity profiles, and therapeutic efficacy. Moreover, the review addresses challenges and patent issues in the synthesis of deuterated indoles and highlights their potential applications in precision medicine. In the future, deuterated indoles may positively impact therapy and contribute to advances in precision medicine through molecular engineering.