Metabolic syndrome is a pathological condition of public health importance caused by the co-occurrence of several metabolic illnesses, such as atherogenic dyslipidemia, obesity, insulin resistance, and systemic hypertension; this condition affects about 20–30% of the world’s population. Although more is being explored to understand the underpinning molecular mechanisms, such as oxidative stress, circulating free fatty acids, and inflammation, more research is needed to unravel better therapeutic options. The current therapeutic techniques for treating metabolic syndrome rely on the strategy of exploring treatment with different pharmaceuticals for the individual components, such as dyslipidemia, hypertension, and type II diabetes, as well as any related comorbidities. Such treatment options have been met with insufficient patient adherence and drug-drug interactions, ultimately leading to suboptimal illness management. Target-specific bioactive compounds such as luteolin, curcumin, resveratrol, quercetin, and others derived from natural resources such as plants and vegetables have proved to be beneficial against the comorbidity over the years however, due to minimizing effect of their poor bioavailability, fast metabolism, and poor water solubility on their in vivo effectiveness, their therapeutic utility has become lessened. Various nanotechnology-based pharmaceutical approaches such as lipid-based emulsion systems, solid dispersion, and micronization have recently improved the lessened therapeutic utility. These nanoformulations of plant compounds have been discovered to have the ability to bridge the gap between the pharmacological ineptitude and therapeutic results of these bioactive compounds when compared to the traditional drug delivery methods. This chapter explores the literature on the development of various plant-based nanoformulations and their multi-target approach against metabolic syndrome. It also addresses the possible limitations in nanoformulation development.