Plants are a source of numerous secondary metabolites (SMs) that are required by them to adapt and survive in the extremities. These metabolites being the by-products of primary metabolites help plants to withstand multiple biotic and abiotic stresses like pathogens, predators, drought, salinity, UV radiation, thermal, temperature, etc. Plant growth and productivity are largely affected by the endogenous levels of these metabolites. The type and endogenous levels of these metabolites depends on several factors like species, genotype, physiology, and environmental factors, etc. SMs comprise of three main groups: phenolics, nitrogen-containing compounds, and terpenes. To combat the detrimental effects of abiotic stressors, plants undergo rapid shifts in SMs biosynthesis and accumulation. As a result, SMs have a strong association with plants’ ability to survive environmental stressors. Several chemical compounds, including phytohormones have been utilized as exogenous treatments to improve plant tolerance to various stressors. This chapter highlights the SMs mediated defense responses and details the probable mechanism behind the crosstalk between phytohormones/plant growth regulators (PGRs) and various environmental stresses.