Since the discovery of coenzyme of NAD+ by Sir Arthur Harden and William John Young in 1904, coenzyme I (NAD+ and NADH) and coenzyme II (NADP+, NADPH) and their precursors NR and NMN have been continuously paid attention by scientists to study their metabolic processes and mechanisms of action in organisms. In recent years, more and more scientists have carried out research on the application of nicotinamide coenzymes in the treatment of diseases and the alleviation of aging. Considering the important physiological functions and application value of coenzyme I and coenzyme II and their precursors, their synthesis and large-scale preparation methods have attracted the attention of the scientific community and industry. A variety of synthetic methods have been reported for more than 100 years. The synthesis and preparation methods of nicotinamide coenzyme and its precursors (including NR, NMN, NAD+, NADH, NADP+, and NADPH) reported in the literature include fermentation extraction, chemical synthesis, enzymatic synthesis, electrochemical synthesis, and synthetic biology. This chapter attempts to make a systematic summary of the synthesis and preparation of these nicotinamide coenzymes and their precursors.