Background <p>Coenzyme Q₁₀ (CoQ₁₀) plays a vital role in mitochondrial bioenergetics and functions as a potent endogenous antioxidant. Low CoQ₁₀ levels have been associated with various neurodegenerative, metabolic, muscular, and cardiovascular disorders. Early intervention with high-dose oral CoQ₁₀ (5–50 mg/kg/day) can mitigate disease progression and delay the onset of renal disease. We recently developed an emulgel matrix that facilitates the ingestion of high-dose, oil-dissolved CoQ₁₀ for patients with CoQ₁₀ deficiency and secondary dysphagia.</p> Objective <p>To evaluate the bioavailability and cellular compatibility of this novel CoQ₁₀ emulgel.</p> Methods <p>Two exploratory studies were conducted in healthy adults: a randomized cross-over single-dose trial (<i>n</i> = 6) and a 14-day repeated-dose trial (<i>n</i> = 12) comparing 1&#xa0;g of CoQ₁₀ administered as emulgel (25 g serving) or solid capsules (2 × size-00). Plasma CoQ₁₀ concentrations were determined by validated HPLC-UV and pharmacokinetic parameters were analyzed using noncompartmental methods. Cellular compatibility was assessed in Vero cells.</p> Results <p>The single-dose study in healthy adults demonstrated equivalent bioavailability of 1&#xa0;g CoQ₁₀ administered via emulgel (25 g serving) and solid capsules (1&#xa0;g CoQ₁₀ in two size-00 capsules). However, CoQ₁₀ in the emulgel exhibited faster and more efficient absorption. A 14-day repeated-dose study revealed significant higher plasma CoQ₁₀ concentrations with emulgel administration, potentially achieving therapeutic levels. A cellular compatibility assay confirmed the safety of the emulgel.</p> Conclusions <p>These findings indicate that the emulgel matrix does not compromise the bioavailability of oil-dissolved CoQ₁₀ and offers a promising, safe, and comfortable alternative for patients with dysphagia requiring long-term, high-dose CoQ₁₀ supplementation.</p>