Background: The short QT syndrome (SQTS) is rare inherited channelopathy associated with marked shortening of QT interval resulting from an accelerated cardiac repolarization. Patients are prone to atrial and ventricular tachyarrhythmia and have a high risk for sudden cardiac death (SCD). The SQT1, SQTS variant, results from a gain-of-function N588K-KCNH2 mutation in the rapid delayed rectifier potassium current (IKr) channels. Since β-Adrenoceptor blocker can block slow delayed rectifier potassium currents (IKs) and IKr, we used in silico approach to evaluate carvedilol’s electrophysiological effects on SQT1. Methods and Resutls: Contemporary mathematical models of human ventricular action potential (AP) developed by ten Tusscher et al. were modified to incorporate a Markov chain formulation of IKr describing the SQT1 mutant condition. Cellular action potential models were incorporated into a transmural strand for investigation of QT interval changes. In addition, the simulated IKs and IKr inhibition to prolong the QT interval in SQT1 condition was quantified. The blocking effects of carvedilol on IKs and IKr were modelled by using Hill coefficient and IC50 from literatures (10 μM carvedilol reduced IKr in Wild Type- and N588K-KCNH2 by 92.8% and 36.0%; it reduced IKs by 36.5% in both conditions). At the single cells, carvedilol prolonged the action potential duration (APD) in SQT1 condition; at the strand level, the effects of carvedilol normalized the QT interval in SQT1 from 286 ms to 364 ms. Conclusions: Computational simulations identified β-Adrenoceptor blocker carvedilol as a potential drug of choice for SQTS treatment.