This comprehensive review explores the development of silk nanoformulations, emphasizing their potential applications in biomedical fields and environmental sustainability. Silk fibroin, derived from silkworms, exhibits remarkable biocompatibility and biodegradability, making it an ideal candidate for various applications, including drug delivery, tissue engineering, and environmental remediation. The review highlights advanced fabrication techniques such as electrospinning, which allows for the production of nanofibers with tailored properties for specific applications. Additionally, sericin-based nanoformulations are discussed, showcasing their role in cancer therapy and regenerative medicine, while also addressing challenges in scaling production and ensuring quality. The paper underscores the importance of understanding the environmental implications of these materials, advocating for further research to assess their long-term impacts and optimize their life cycle. Ultimately, the review positions silk nanoformulations as a promising frontier in material science, bridging nature-inspired solutions with cutting-edge nanotechnology.