Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory disease classified as an oral potentially malignant disorder (OPMD) and increased transformation risk to oral cancer. Oral lichenoid reactions (OLRs) share the clinical manifestations of OLP. This study aimed to determine histomorphometric changes in OLPs and OLRs in comparison to the healthy control, which helps to plan for the establishment of diagnostic criteria. This cross-sectional prospective study was conducted on a total of 75 tissue-embedded paraffin-block samples, including OLPs (n = 25), OLR cases (n = 25), and healthy control individuals (n = 25). The study groups were compared by chi-squared, Fisher's exact, and one-way ANOVA tests. A p-value less than 0.05 was considered statistically significant. Comparison of the nuclear area and cellular area showed a statistically significant difference between study groups in basal and parabasal layer (P < 0.05). Comparison of the nuclear-to-cytoplasm ratio showed a statistically significant difference between study groups in basal (P < 0.05) but not in the parabasal region (P = 0.681). We showed a significant difference in the nuclear and cellular area, nuclear-to-cytoplasm ratio between OLPs and OLRs, and healthy controls, but there was no statistically significant difference between OLPs and OLRs. Thus, these parameters cannot be applied to differentiate diagnoses between OLPs and OLRs.