We sought to assess the impact of telemedicine on healthcare utilization and medical expenditures among patients with a diagnosis of gastrointestinal (GI) cancer. Patients with newly diagnosed GI cancer from 2013 to 2020 were identified from the IBM MarketScan database (IBM Watson Health) . Healthcare utilization, total medical outpatient insurance payments within 1 year post-diagnosis, and out-of-pocket (OOP) expenses among telemedicine users and non-users were assessed after propensity score matching (PSM). Among the 32,677 patients with GI cancer (esophageal, n = 1862, 5.7%; gastric, n = 2009, 6.1%; liver, n = 2929, 9.0%; bile duct, n = 597, 1.8%; pancreas, n = 3083, 9.4%; colorectal, n = 22,197, 67.9%), a total of 3063 (9.7%) utilized telemedicine. After PSM (telemedicine users, n = 3064; non-users, n = 3064), telemedicine users demonstrated a higher frequency of clinic visits (median: 5.0 days, IQR 4.0–7.0 vs non-users: 2.0 days, IQR 2.0–3.0, P < .001) and fewer potential days missed from daily activities (median: 7.5 days, IQR 4.5–12.5 vs non-users: 8.5 days, IQR 5.5–13.5, P < .001). Total medical spending per month and utilization of emergency room (ER) visits for telemedicine users were higher vs non-users (median: $10,658, IQR $5112–$18,528 vs non-users: $10,103, IQR $4628–$16,750; 46.8% vs 42.6%, both P < .01), whereas monthly OOP costs were comparable (median: $273, IQR $137–$449 for telemedicine users vs non-users: $268, IQR $142–$434, P = .625). Telemedicine utilization was associated with increased outpatient clinic visits yet reduced potential days missed from daily activities among patients with GI cancer. Telemedicine users tended to have more ER visits and total medical spending per month, although monthly OOP costs were comparable with non-users.