Since time immemorial, medicinal plants have been the treasure trove of bioactive compounds with therapeutic potential and are prescribed under diverse traditional healthcare systems. Nanoformulations originating from medicinal plants have shown to be a breakthrough in medicine, as the promise of improved therapeutic effects, drug targeting, and bioavailability in this context is prevailing. The nanoparticles (NPs), liposomes, and dendrimers are included in the nanoformulations. These will offer advantages in the form of phytochemicals with improved bioavailability and controlled release as well as targeted delivery; however, despite such hopeful benefits, broad limitations and challenges blunt their application at large. Primarily, due to the plant origin, variability, and complexity in the chemical composition of active constituents, by default, it is hard to standardize and control quality. Additionally, factors affecting environmental stability also determine whether or not NPs made from plants are stable; thus, their healing power is called into question. In addition to these concerns regarding consistency and reproducibility during technical challenges in production scaling, questions about the safety of nanomaterials are raised. Production and development regulations are not standardized! Reforming the formation of commercialization is necessary. Research realizes that these critical limitations challenge the production, safety, efficacy, and scalability of medicinal plant nanotherapeutics. This chapter describes scale-up production, benefits, applications, limitations, challenges, mechanisms of toxicity, and strategies for mitigating the toxicity of plant-based nanoformulations and focuses on the present scenario and some recommendations.