Alternative medicine for complex diseases explores multiple strategies and targets in search of unconventional relief or treatment approaches. Understanding complex diseases is challenging due to the interplay of various comorbidities, genetic, lifestyle, and environmental factors. The limitation of single-drug therapies for complex diseases usually demands drug combinations, complementary (use of a non-mainstream approach in conjunction with conventional medicine), or alternate medicine (use of a non-mainstream approach instead of conventional medicine). Alternate therapeutics that target multiple molecular networks underlying complex diseases could enhance treatment efficacy. However, there are concerns about the accompanying adverse interactions or toxicity in this practice. Clinically significant non-drug interactions from complementary and alternative medicine could impact absorption, distribution, metabolism, excretion, and pharmacological effects. This chapter covers non-drug interactions with a focus on the modalities of alternative medicine.