Context: Dietary botanicals are often consumed together with allopathic medicines, which may give rise to pharmacokinetic interactions. In vitro intestinal models are useful to identify botanical-drug interactions, but they may exhibit different expressions of transporters or enzymes. Objective: To compare the effects of selected dietary botanical extracts on cimetidine transport across two in vitro intestinal models. Materials and Methods: Bi-directional transport of cimetidine was measured across Caco-2 cell monolayers and excised porcine jejunum tissue in the absence (control) as well as the presence of verapamil (positive control) and selected plant extracts. Results: Sclerocarya birrea Hochst. (Anacardiaceae) (marula) and Psidium guajava L. (Myrtaceae) (guava) crude extracts significantly decreased cimetidine efflux in both in vitro models resulting in increased absorptive transport of the drug. On the other hand, Dovyalis caffra Sim. (Flacourtiaceae) (Kei apple), Prunus persica (L.) Batsch (Rosaceae) (peach), Aspalathus linearis (Burm. f.) R. Dahlgren (Rabaceae) (rooibos tea), Daucus carota L. (Apiaceae) (carrot), Prunus domestica A. Sav. (Rosaceae) (plum), Beta vulgaris L. (Chenopodiaceae) (beetroot) and Fragaria x ananassa (Weston) Duchesne ex Rozier. (Rosaceae) (strawberry) crude extracts exhibited different effects on cimetidine transport between the two models. Discussion: Caco-2 cells were more sensitive to changes in cimetidine transport by the plant extracts and therefore may overestimate the effects of co-administered plant extracts on drug transport compared to the excised pig tissue model, which is congruent with findings from previous studies. Conclusion: The excised porcine jejunum model seemed to provide a more realistic estimation of botanical drug pharmacokinetic interactions than the Caco-2 cell model.