This study designed a set of computerized collaboration scripts for multi-touch supported collaborative design-based learning and evaluated its effects on multiple aspects of metacognitive self-regulation in terms of planning and controlling and mathematical literacy achievement at higher and lower levels. The computerized scripts provided a sequence of guidance for structuring intragroup and intergroup interactions and prompting individual metacognitive processes throughout the collaborative design phases based on the Think-Pair-Share method. Four intact classes of 80 fifth-grade students participated in this study. Employing a nonequivalent comparison group quasi-experimental design, this study examined whether or not applying the scripts better enhanced self-regulation and achievement in a technology-infused mathematics learning classroom. Multivariate analyses were conducted to reveal the effects on the aspects among the two sets of variables. The results showed medium effects on the controlling of metacognitive self-regulation and higher level achievement, whereas no significant effects were found for the planning aspect and lower level achievement between the groups with and without the collaboration scripts. The implications of this work in relation to metacognitive processes and technology-infused mathematics learning are discussed based on the results.