Traditional medicine is widely accepted as a complementary approach to modern medicine for the treatment of human disease. The use of herbal medicines and their active ingredients played a crucial role in the formation of many modern drugs. Approximately 65% of all approved drugs and 77% of the total small molecules used for cancer treatment are originally derived from natural products. Nutraceuticals are dietary compounds with health benefits, few side effects, and high efficacy. Recently, it was reported that the use of herbal plant extracts with a nutraceutical mixture can produce potent anticancer activity in mammals. The suspensions that contain the plant extract from Arum palaestinum, Peganum harmala and Curcuma longa with nutraceutical components harmine, isovanillin, and curcumin show selective inhibition of cancer growth without any observable toxicity towards normal tissue. GZ17–6.02, a combination of curcumin, harmine, and isovanillin is superior compared to other single agents and suspensions in anticancer efficacy with an effective dose 50 (ED50) of 50 μg/mL and eventually led to Phase-I clinical trial for patients with advanced solid organ tumors or lymphoma. In pursuit of discovering a better therapeutic agent, a novel reaction was revealed to take place between harmaline and isovanillin producing the dimeric scaffold with a higher anti-tumor activity than GZ17–6.02. The dissertation describes herein the structure-based design and synthesis of a series of novel harmaline analogs based on this chemistry and establishes structure-activity relationships for this scaffold in the light of relevant structural, biochemical, spectroscopic, and cell-based studies.