In the field of medicine, diagnosing diseases involves various steps, procedures, and protocols. Histopathological examination remains the gold standard for a definitive and accurate diagnosis. This process relies on an initial step of tissue fixation.Formaldehyde is a traditional fixative material and is typically used as 10% or 4% buffered solutions. However, significant health risks are associated with formaldehyde exposure.Our paper aimed to evaluate and compare variable media as a preservative agent. The study included eight groups as follows: (1) normal saline 0.9%; (2) local anesthesia with epinephrine (2% Lidocaine HCl/ 1:100,000 epi); (3) local anesthesia without epinephrine (3% Mepivacaine HCl/ plain); (4) distilled water; (5) Saliva collected from healthy male participants; (6) Milk (Almarai- full-fat fresh milk); (7) Propolis; and (8) l0% formalin. Three tissue samples from each group were fixed in 10% formalin for 24 h after being preserved for 6 h at ambient temperature in their respective media. All specimens were stained with Hematoxylin and Eosin.The following histological structures were assessed: (1) superficial 1/3 of the epithelium, (2) middle 1/3 of the epithelium, (3) lower 1/3 of the epithelium, (4) basement membrane/rete ridges, (5) fibrous connective tissue, (6) blood vessels/endothelial cells, (7) skeletal muscle, (8) adipose tissue, and (9) nerve bundles. A numerical rating system was employed to assess these components, with scores ranging from 1 to 4.Our findings suggest propolis has promising potential as a tissue fixative. This study highlighted the effectiveness of propolis as a preservative and fixative solution, which warrants further investigation.