Carvedilol (CARV) is a widely used drug, which has shown low oral bioavailability. Lipid-based drug delivery systems (LBDDS) appear as promising alternatives to overcome CARV pharmacokinetic issues. Despite the pharmaceutical potential of LBDDS, the lipids used in these systems present stability issues and their use demands caution. This study set out to evaluate different lipid vehicles for CARV in terms of their ability to dissolve the drug and preserve its stability in LBDDS. The CARV solubility was determined in nine commonly used lipid excipients. Thermal and spectroscopic analysis (DSC, TG, FTIR), and accelerated stability studies were used to characterize drug-excipient interaction. CARV has highest solubility in polyethoxylated castor oil (PcasO), castor oil (CasO) and caprylic/capric triglycerides (CCT), ranging from 70 to 4 mg mL−1. DSC and FTIR analyses showed evidence of drug-oil interaction. TG results gained in inert and oxidative atmosphere showed that these interactions lead to a drug stability loss at temperatures above 300 °C, especially in binary mixtures of CARV with CCT, sesame oil (SesO) and CasO. On the other hand, in accelerated stability studies performed at 50 °C, CARV solutions in CCT and SesO were the most stable systems. The results of this study showed that CARV had high solubility and stability in PcasO. This means that PcasO is suitable for systems demanding high drug concentration and which are produced at high temperatures. On the other hand, SesO and CCT can give rise to less concentrated systems which can be stable when produced at low temperatures.