Secondary metabolites (PSMs) of plants are large group of highly diversified organic compounds which do not directly participate in plant primary metabolism, growth, development or reproduction but serve several important functions for the plant, interact with other plants, and are increasingly being used in human therapeutics. In this detailed review, the chemical profile of the most important classes of PSMs (alkaloids, phenolics, terpenoids and sulfur compounds) is discussed, and questions concerning their biosynthetic pathways, regulatory mechanisms and their pharmacological relevance are raised. A systematic literature review was conducted according to PRISMA guidelines, including 94 peer-reviewed publications from 2001 to 2018. We found that the structural diversity of PSM could be extremely dependent on plant species, environmental conditions (UV radiation, temperature, pressure due to herbivores, etc) and peculiar biosynthetic route networks (shikimate, mevalonate and mevalonate-independent routes). Next, a critical comparison between the different extraction techniques was made based on the efficiency of the bioactive constituent(s) recovery, namely conventional Soxhlet extraction method and other emerging methods such as microwave-assisted extraction and supercritical fluid extraction. They have been used in therapeutic applications such as anticancer mechanisms), antimicrobial activity, modulation of antioxidant defence mechanisms, neuroprotection, metabolic regulation. The review concludes with a summary of the gaps in knowledge regarding metabolomics, synthetic biology and translation to clinical applications of PSM based therapeutics, and the recommendations for future research.