GS may cause mild and reversible gastrointestinal side effects in some cases. In one trial, people with peptic ulcers and those taking diuretic drugs were more likely to experience such side effects.⁵

In a preliminary study, glucosamine supplements appeared to raise intra-ocular (eyeball) pressure by an average of about 3 mm Hg in people who had elevated intra-ocular pressure or a certain type of glaucoma (open-angle glaucoma).⁶ Therefore, individuals who have, or are at risk of developing, glaucoma should be monitored by a doctor if they wish to take glucosamine.

Animal research has raised the possibility that glucosamine could contribute to insulin resistance.^{7, 8} This effect might theoretically result from the ability of glucosamine to interfere with an enzyme needed to regulate blood sugar levels.⁹ However, available evidence does not suggest that taking glucosamine supplements will trigger or aggravate insulin resistance or high blood sugar.^{10, 11} Two large, 3-year controlled trials found that people taking GS had either slightly lower blood glucose levels or no change in blood sugar levels, compared with people taking placebo.^{12, 13} Until more is known, people taking glucosamine supplements for long periods may wish to have their blood sugar levels checked; people with diabetes should consult with a doctor before taking glucosamine and should have blood sugar levels monitored if they are taking glucosamine.

In 1999 the first case of an allergic reaction to oral GS was reported.¹⁴ Allergic reactions to this supplement appear to be rare.