<p>This study investigates the influence of high-entropy oxide (HEO) fine powder with submicron agglomerates (Mg₀.₂Ni₀.₂Co₀.₂Cu₀.₂Zn₀.₂O) on the mechanical performance, microstructural development, and durability characteristics of cement-based mortars. HEO was synthesized via a modified sol–gel method and incorporated into mortar mixtures as an additional additive at dosages of 0–1.0 wt% relative to the cement content. The experimental results demonstrate a strong dosage-dependent behavior. The optimum performance was obtained at 0.25 wt% HEO, where compressive and flexural strengths increased by up to approximately 3–4% compared to the control sample. In contrast, higher dosages (≥ 0.75 wt%) resulted in a gradual reduction in mechanical performance, indicating a threshold beyond which HEO begins to negatively affect hydration-related processes. Microstructural analysis (XRD and SEM–EDS) revealed that HEO particles contribute to matrix densification through a filler effect and act as nucleation sites for hydration products, leading to a more compact cementitious structure at optimal content. However, excessive incorporation appears to disrupt hydration continuity due to particle agglomeration and dilution effects. Durability tests showed improved resistance to water absorption, chloride ion penetration, and corrosion current with increasing HEO content, attributed to pore refinement and reduced ion transport pathways. The most balanced performance in both mechanical and durability properties was achieved at low HEO dosage. Overall, high-entropy oxides demonstrate significant potential as nano-scale additives for cementitious systems; however, their effectiveness is highly dependent on dosage, with low replacement levels providing the most beneficial performance balance.</p>