Silk protein has been used in various scientific and industrial fields owing to its enhanced mechanical properties, in vivo biocompatibility, biodegradability, stability, and low toxicity. The silk protein, generally obtained from silkworms or spiders, is basically composed of sericin the hydrophilic chain, and fibroin the amphiphilic chain which provides mechanical strength to the silk. Silk NPs can be produced using various methods such as desolvation, electrospraying, salting out, supercritical fluid technologies, microemulsion, and self-assembly methods. Nanotechnology has improved the properties of silk by providing size control, morphology control, modifiability with functional groups for targeting, release control, and mechanical and thermal control of silk NPs. Nanotechnology also contributed to the usage of silk in the fields of drug delivery, wound healing, biosensors, bioelectronic tools, biomedical implants, gene therapy, environmental waste treatment, etc. However, there are still concerns about silk NPs’ scalability, size consistency, and some chemical usage in production. The mentioned drawbacks should be investigated thoroughly, and the way should be paved for the safe and effective application of silk NPs in wider areas of the clinic. Herein, we examined the silk protein incorporated in nanotechnology and their potential applications mentioned above.