Aim: This study aimed to alleviate dengue virus (DENV)-mediated fibrosis in a chick embryo model using ultradiluted Eupatorium perfoliatum (UEP). Materials & methods: Chorioallantoic membrane and liver of infected embryonated chicken eggs were checked for DENV pathogenesis. Cytotoxicity of UEP was assessed by MTT and scratch assay. Cytopathic assay after DENV infection was performed in vitro to check the effect of UEP and its constituents. Histopathology analysis revealed DENV-mediated fibrosis and the effect of UEP. qRT-PCR and gelatin zymography showed levels of fibrosis-causing genes. Results: UEP showed low cytotoxicity and maximum potential in mitigating DENV-mediated fibrosis in vivo via regulation of fibrosis biomarkers TGF-β, MMP-1, MMP-9, TIMP-1 and IFNs. Conclusion: UEP may be considered to alleviate DENV-mediated pathogenesis.