Resistant maltodextrin (RMD) from various sources of starch has been extensively studied. However, studies which reported the effects of tapioca RMD (TRM) on glucose and insulin response are lacking. This study investigated the effect of TRM on postprandial plasma glucose and serum insulin in healthy subjects. Additionally, satiety and gastrointestinal tolerability were also evaluated. Sixteen healthy participants received five different treatments on five separate days. Participants received 50 g of either: glucose (GL), tapioca maltodextrin (TM), TRM, MIX15% (7⋅5 g TRM + 42⋅5 g TM) or MIX50% (25 g TRM + 25 g TM). Plasma glucose, serum insulin and subjective appetite responses were measured postprandially over 180 min. Gastrointestinal symptoms were evaluated by questionnaire before and after each test day. Results showed that at 30 min after treatment drinks, plasma glucose after TRM was significantly lowest (104⋅60 (sem 2⋅63 mg/dl) than after GL (135⋅87 (sem 4⋅88) mg/dl; P <0⋅001), TM (127⋅93 (sem 4⋅05) mg/dl; P = 0⋅001), MIX15% (124⋅67 (sem 5⋅73) mg/dl; P = 0⋅039) and MIX50% (129⋅33 (sem 5⋅23) mg/dl; P = 0⋅003) (1 mg/dl = 0⋅0555 mmol/l). In addition, TRM also significantly reduced serum insulin (13⋅01 (sem 2⋅12) μIU/ml) compared with GL (47⋅90 (sem 11⋅93) μIU/ml; P = 0⋅013), TM (52⋅96 (sem 17⋅68) μIU/ml; P = 0⋅002) and MIX50% (33⋅16 (sem 4⋅99) μIU/ml; P = 0⋅008). However, there were no significant differences in subjective appetite between treatments (P > 0⋅05). A single high dose of TRM (50 g) caused flatulence (P < 0⋅05). Tapioca resistant maltodextrin has low digestibility in the small intestine and, therefore, reduced incremental plasma glucose and serum insulin, without affecting satiety in healthy subjects over 180 min. Gastrointestinal tolerability of TRM should be considered when consumed in high doses.