<p>Asthma is a chronic disease associated with airway inflammation and hyper-responsiveness. In developing countries morbidity and mortality remain high, mainly due to issues with affordability and availability of treatment options and disparities in healthcare delivery. With the increasing dependence on herbal medicines, research focus has shifted to evaluating indigenous treatments and plants with acclaimed medicinal uses. <i>Eleusine indica</i> is an annual grass with widely reported benefits including asthma and other pulmonary disorders. In this study, we assess the reported anti-asthmatic properties of <i>Eleusine indica</i> in ovalbumin-induced airway inflammation in guinea pigs. We assess the inhibitory effect of the ethanolic extract on allergen-induced white blood cell proliferation, serum expression of pro-inflammatory mediators and histological features associated with allergic airway inflammation. <i>Eleusine indica (EI)</i> at 400 and 600&#xa0;mg/kg significantly inhibited neutrophil and eosinophil proliferation associated with ovalbumin challenge. Guinea pigs treated with EI showed no elevations in serum levels of intercellular cell adhesion molecule-1 and interleukin-8 compared to saline-treated, ovalbumin-challenged control guinea pigs. Histopathological scores and morphometric analysis of lung tissue showed significant reductions in inflammatory cell infiltration, bronchial smooth muscle hypertrophy and goblet cell hyperplasia in <i>Eleusine indica</i>-treated guinea pigs. Taken together, the results show that <i>Eleusine indica</i> possesses significant anti-asthmatic properties. It mitigated key molecular and histological markers of allergic airway inflammation. Our findings support its traditional use in the management of airway inflammation associated with allergic asthma.</p> Graphical abstract <p></p>