The aim of this trial was to evaluate the effects of alpha-lipoic acid (ALA) and gamma-linolenic acid (GLA) and the beneficial effect of physical exercise on positive sensory symptoms and neuropathic pain in patients with compressive radiculopathy syndrome from disc-nerve root conflict. Often these painful syndromes after the acute event, tend to recurr becoming subacute or chronic syndromes that become for the period of interest disabiling is an event very important in these cases proper prevention, based on a maintenance drug therapy and the strengthening exercises of paravertebral muscles, flexibility exercises on the spine and when needed on the reduction of body weight. In this Observational Cohort, two-arm trial, 203 patients were enrolled and divided into two groups, the first, ALA and GLA group, (n = 101) received oral dose of 600 mg of alpha-lipoic acid (ALA) and 360 mg of gamma-linolenic acid (GLA) and a rehabilitation program for six weeks, the second (n = 102) treated with only rehabilitation program. Patients were recruited at the centre of Physical Medicine and Rehabilitation, they underwent a physiatric examination at the primary outcome (t0) and secondary outcomes were recorded at monitoring visits scheduled at two weeks = t1, four weeks = t2, six weeks = t3, and at the same has been administered the following scale: VAS scale, SF-36, Oswestry Low Back Pain Disability Questionnaire, Aberdeen Back Pain Scale (ABPS), Revised Leeds Disability Questionnaire (LDQ), Roland and Morris Disability Questionnaire. Significant improvements was noted in the ALA and GLA group for paresthesia, stabbing and burning pain, as showed by VAS (Visual Analogue Scale), Oswestry Low Back Pain Disability Questionnaire, Aberdeen Low Back Pain Scale; also, improvements of quality of life has been noted, in the same group, as showed by SF-36, LDQ (Revised Leeds Disability Questionnaire), Roland and Morris disability questionnaire. All these outcome measure showed statistically significant decreases. Oral treatment with alpha-lipoic acid (ALA) and gamma-linolenic acid (GLA) for six weeks in synergy with rehabilitation therapy improved neuropathic symptoms and deficits in patients with radicular neuropathy.