Chronic venous disease (CVD) significantly impacts global health, presenting a complex challenge
in medical management. Despite its prevalence and the burden it places on healthcare systems, CVD remains
underdiagnosed and undertreated. This review aims to provide a comprehensive analysis of the bioactive compounds
in the Citrus genus, exploring their therapeutic potential in CVD treatment and addressing the gap in
current treatment modalities. A narrative review methodology was adopted, focusing on the pharmacological
effects of Citrus-derived bioactive compounds, including flavonoids and terpenes. Additionally, the review introduced
the DBsimilarity method for analyzing the chemical space and structural similarities among Citrus
compounds. The review highlights the Citrus genus as a rich source of pharmacologically active compounds,
notably flavonoids and terpenes, which exhibit significant anti-inflammatory, antioxidant, and veno-protective
properties. Some of these compounds have been integrated into existing therapies, underscoring their potential
for CVD management. The DBsimilarity analysis further identified many clusters of compounds with more
than 85% structural similarity. Citrus-derived bioactive compounds offer promising therapeutic potential for
managing CVD, showcasing significant anti-inflammatory, antioxidant, and veno-protective effects. The need
for further comparative studies, as well as safety and efficacy investigations specific to CVD treatment, is evident.
This review underlines the importance of advancing our understanding of these natural compounds and
encouraging the development of novel treatments and formulations for effective CVD management. The DBsimilarity
method's introduction provides a novel approach to exploring the chemical diversity within the Citrus
genus, opening new pathways for pharmacological research.