Low‐volume sampling devices offer the promise of lower discomfort and greater convenience for patients, potentially reducing patient burden and enabling decentralized clinical trials. In this study, we determined whether low‐volume sampling devices produce pharmacokinetic (PK) data comparable to conventional venipuncture for a diverse set of monoclonal antibodies (mAbs) and small molecules. We adopted an open‐label, non‐randomized, parallel‐group, single‐site study design, with four cohorts of 10 healthy subjects per arm. The study drugs, doses, and routes of administration included: crenezumab (15 mg/kg, intravenous infusion), etrolizumab (210 mg, subcutaneous), GDC‐X (oral), and hydroxychloroquine (HCQ, 200 mg, oral). Samples were collected after administration of a single dose of each drug using conventional venipuncture and three low‐volume capillary devices: TassoOne Plus for liquid blood, Tasso‐M20 for dry blood, both applied to the arm, and Neoteryx Mitra® for dry blood obtained from fingertips. Serum/plasma concentrations from venipuncture and TassoOne Plus samples overlapped and PK parameters were comparable for all drugs, except HCQ. After applying a baseline hematocrit value, the dry blood concentrations and PK parameters for the two monoclonal antibodies were comparable to those obtained from venipuncture. For the two small molecules, two bridging strategies were evaluated for converting dry blood concentrations to equivalent plasma concentrations. A baseline hematocrit correction and/or linear regression‐based correction was effective for GDC‐X, but not for HCQ. Additionally, the study evaluated the bioanalytical data quality and comparability from the various collection methods, as well as patient preference for the devices.