The efficacy of Cuban sugarcane-extracted policosanol (Raydel), a purified blend of eight long-chain aliphatic alcohols, was compared to copycat sugarcane-extract powder (SCEP) to assess their effects on dyslipidemia, oxidative stress, and vital organs of zebrafish under the influence of a high-cholesterol diet (HCD). Zebrafish were fed with HCD (final 4%, /) or HCD infused with policosanol (PCO, final 1%, /) or SCEP (final 1%, /). Post 14-week consumption, blood and organs were harvested and processed for various biochemical, histological, and immunohistochemical (IHC) examinations, and fluorescent staining. Following 14-week consumption, the PCO-supplemented group exhibited higher zebrafish survival probability than the SCEP-supplemented group. Both PCO and SCEP substantially impacted the HCD-disrupted plasma lipid profile; however, PCO supplementation exhibited a significantly better effect than SCEP. Similarly, PCO supplementation significantly improved the blood glucose level, hepatic function biomarkers, and oxidative-antioxidant balance disturbed by HCD. PCO supplementation displayed a substantial inhibitory effect against HCD-induced fatty liver changes, nephromegaly, and cellular senescence. Likewise, PCO effectively protected the brain against HCD-induced apoptosis and accumulation of 4-hydroxynonenal (4-HNE); in contrast, SCEP supplementation showed almost no effect in reducing such adverse changes. The comparative findings between PCO and SCEP highlight the protective effects of PCO against HCD-induced oxidative stress and dyslipidemia via the enhancement of antioxidant markers, leading to protection of the liver, kidney, and brain, while SCEP failed to achieve similar outcomes.