We examined the effect of a dietary seaweed extract-sulfated xylorhamnoglucuronan (SXRG84)-on individuals with inflammatory skin conditions. A subgroup analysis of a larger trial was undertaken, where 44 participants with skin conditions were enrolled in a double-blind placebo-controlled crossover design. Subjects ingested either SXRG84 extract (2 g/day) for six weeks and placebo for six weeks, or vice versa. At baseline, six- and twelve-weeks inflammatory markers and the gut microbiota were assessed, as well as skin assessments using the dermatology quality of life index (DQLI), psoriasis area severity index (PASI) and visual analogue scales (VAS). There were significant differences at weeks six and twelve for pro-inflammatory cytokines IFN-γ ( = 0.041), IL-1β ( = 0.030), TNF-α ( = 0.008) and the anti-inflammatory cytokine IL-10 ( = 0.026), determined by ANCOVA. These cytokines were all significantly higher at six weeks post placebo compared to twelve weeks post placebo followed by SXRG84 treatment. A total of 23% of participants reported skin improvements, as measured by VAS (mean difference 3.1, = 0.0005) and the DQLI score (mean difference -2.0, = 0.049), compared to the 'non-responders'. Thus, the ingestion of SXRG84 for 6 weeks reduced inflammatory cytokines, and a subset of participants saw improvements.