<p>Cosmetics are essential to daily hygiene and self-confidence, yet improper use can lead to significant dermatological complications. This study assessed cosmetic use behaviors, safety practices, and the prevalence of adverse effects among female university students in Palestine. A cross-sectional survey was conducted among 803 female students at An-Najah National University (June 2023–May 2024). Data on demographics, usage patterns, safety behaviors, and self-reported side effects were collected via a validated questionnaire. Multivariable logistic regression identified independent predictors of adverse reactions. While 79.2% of participants selected products based on skin type and 70.6% purchased from professional outlets, critical safety gaps were identified: 73.7% did not consult specialists, 63.9% skipped allergy tests, and 40% used expired products. The most prevalent adverse effects were skin irritation (31.6%) and acne (26.1%). Long-term use (&gt; 3 years) was significantly associated with acne (<i>p</i> = 0.010) and clogged pores (<i>p</i> = 0.009). Multivariable analysis revealed that daily use (aOR = 2.47, 95% CI  1.52–4.01, <i>p</i> = 0.001) and failing to remove makeup before sleep (aOR = 2.16, 95% CI  1.25–3.72, <i>p</i> = 0.006) significantly increased risk. Conversely, selecting products matched to skin type was protective (aOR = 0.62, <i>p</i> = 0.024). Product-specific analysis showed face whiteners had the broadest toxicity profile (<i>p</i> &lt; 0.001). Despite high-risk awareness, unsafe practices-particularly daily exposure and poor bedtime hygiene-drive adverse reactions. Public health efforts should prioritize specialist-led education and skin-type-specific selection over ritualized behaviors like general allergy testing to bridge the gap between awareness and clinical safety.</p>