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Ceramide, a lipid mediator produced in response to stress, plays a critical role in regulating cellular processes such as cell death, differentiation, and insulin sensitivity. This study reveals that ceramide inhibits protein kinase B (PKB/Akt) activation via atypical protein kinase C zeta (PKCζ). In unstimulated cells, PKB and PKCζ form a complex, which dissociates upon insulin stimulation, allowing PKB activation. However, ceramide prevents this dissociation by activating PKCζ, leading to phosphorylation of the PKB-PH domain at Thr34. This modification blocks phosphatidylinositol 3,4,5-trisphosphate (PIP3) binding, thereby inhibiting PKB activation. A T34A-mutated PKB-PH domain, which retains PIP3 binding ability, remains resistant to ceramide-induced inhibition. Inhibition of PKCζ restores PKB activity, underscoring its role in this regulatory pathway. As PKB is essential for cell survival and insulin signaling, ceramide-mediated PKCζ activation represents a potential mechanism contributing to insulin resistance and apoptosis.