Skin illness, with their complicated aetiology and vast spectrum of clinical symptoms, place a significant burden on both patients and healthcare professional’s quality of life. Over the few decades, significant progress has been made in developing effective therapeutic treatments, with a focus on polymeric formulations. Among these, polycaprolactone (PCL) and polyethylene glycol (PEG) have showed promise in treating a variety of skin disorders. This chapter provides a detailed analysis of current advancements in PEG and PCL formulations aimed to treat skin problems. The chapter discusses the physiochemical properties of PEG and PCL, which make them suitable for dermatological applications. Interestingly, these polymers programmable properties such as molecular weight and degradation rates, allow formulations to be adjusted to specific medicinal demands. The chapter then highlights contemporary breakthroughs in PEG-based formulations, such as hydrogels, nanoparticles, and PEGylated pharmaceuticals, designed for the targeted delivery, prolonged drug release, biocompatibility, and biodegradability. In addition, the synergistic effects of PCL with bioactive substances or polymers are investigated, with a focus on mimised side effects and enhanced efficacy. To obtain reliable and regulated drug release kinetics for the treatment of skin illness, numerous strategies for PCL-based delivery system optimisation are addressed, including electrospinning, micro-needle arrays, and composite formulations. Furthermore, the chapter explains how bioactive compounds like peptides, growth factors, and natural products may be introduced to PCL matrices to improve treatment outcomes and promote tissue regeneration. The chapter also includes the preclinical and clinical research that examines the safety and effectiveness of PCL and PEG formulations for the treatment of various skin disorders, such as dermatitis, psoriasis, wounds and skin cancer.