Aim: This review summarizes current evidence regarding increased proteasome and inflammasome activity in response to cellular stress and PTSD-induced neuronal injury. Materials and Methods: A narrative literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar databases. Studies published between 2015 and 2025 were analyzed using keywords including “PTSD,” “proteasome,” “inflammasome,” “NLRP3,” “oxidative stress,” and “neuroinflammation.” Experimental and clinical studies investigating molecular mechanisms associated with PTSD-related cellular stress were included. The reviewed studies demonstrated that chronic traumatic stress promotes excessive activation of the NLRP3 inflammasome and dysregulation of proteasome activity. These changes contribute to accumulation of damaged proteins, mitochondrial impairment, increased reactive oxygen species production, and elevated secretion of pro-inflammatory cytokines, including interleukin-1β and interleukin-18. Persistent activation of these pathways is associated with microglial activation, synaptic dysfunction, impaired neuroplasticity, and progressive neuronal degeneration in PTSD. Conclusions: Proteasome and inflammasome dysregulation play an important role in the neurobiology of PTSD and may contribute to chronic neuroinflammatory and neurodegenerative processes. Targeting these pathways may represent a promising therapeutic strategy for reducing neuronal damage associated with traumatic stress.