Squalane (SQ, a saturated, sebum-mimetic hydrocarbon), oleic acid (OA, a monounsaturated fatty acid), and linoleic acid (LA, a polyunsaturated essential fatty acid) belong to the category of “lipids and fats” in cosmetic materials, and are widely employed as skin-conditioning emollients. However, they present differences in UV stress. In this study, we compared their effects on UV-induced oxidative damage, inflammation, and lipid metabolism using a mouse model and human sebaceous gland cells (SZ95). Results showed that 10% SQ did not worsen oxidative damage or inflammation after 6 weeks of UV exposure. In contrast, the 5% and 10% OA/LA groups showed increased skin wrinkling (p < 0.01), epidermal thickening (p < 0.05), and sebaceous gland atrophy. Transcriptome analysis indicated OA/LA upregulated arachidonic acid-related cytokine pathways (PTGS2/IL-1β; p < 0.001). In SZ95 cells, 0.006% OA/LA significantly increased lipid droplet formation (p < 0.001), free fatty acid (FFA) levels (p < 0.001), and pro-inflammatory gene expression (p < 0.001). Conversely, SQ neither promoted lipid droplet/FFA secretion nor induced oxidative stress. These findings suggest that high concentrations of unsaturated fatty acids in skincare may worsen lipid dysregulation and inflammation, while formulations based on saturated hydrocarbons like SQ could provide superior photoaging management by stabilizing skin barrier function.