Physical activity and exercise are effective approaches in prevention and therapy of multiple diseases. Although the specific characteristics of lengthening contractions have the potential to be beneficial in many clinical conditions, eccentric training is not commonly used in clinical populations with metabolic, orthopaedic, or neurologic conditions. The purpose of this pilot study is to investigate the feasibility, functional benefits, and systemic responses of an eccentric exercise program focused on the trunk and lower extremities in people with low back pain (LBP) and multiple sclerosis (MS). A six-week eccentric training program with three weekly sessions is performed by people with LBP and MS. The program consists of ten exercises addressing strength of the trunk and lower extremities. The study follows a four-group design (N = 12 per group) in two study centers (Israel and Germany): three groups perform the eccentric training program: A) control group (healthy, asymptomatic); B) people with LBP; C) people with MS; group D (people with MS) receives standard care physiotherapy. Baseline measurements are conducted before first training, post-measurement takes place after the last session both comprise blood sampling, self-reported questionnaires, mobility, balance, and strength testing. The feasibility of the eccentric training program will be evaluated using quantitative and qualitative measures related to the study process, compliance and adherence, safety, and overall program assessment. For preliminary assessment of potential intervention effects, surrogate parameters related to mobility, postural control, muscle strength and systemic effects are assessed. The presented study will add knowledge regarding safety, feasibility, and initial effects of eccentric training in people with orthopaedic and neurological conditions. The simple exercises, that are easily modifiable in complexity and intensity, are likely beneficial to other populations. Thus, multiple applications and implementation pathways for the herein presented training program are conceivable. Trial registration: DRKS00020483 (DRKS, German Clinical Trials Register; 24th January 2020 -retrospectively registered; https://www.drks.de/DRKS00020483).