Platelet-rich plasma (PRP) is an alternative to corticosteroid (CS) injections in managing rotator cuff disease. This meta-analysis investigated differences between PRP and CS for function and pain scores in significance and minimal clinical important difference (MCID). A literature search of Ovid Cochrane Library, Medline, Embase, Epub, and Scopus was conducted from inception to October 28, 2021. Eligible studies reported patients older than 18 years with a diagnosis of rotator cuff disease. This review was registered in PROSPERO (ID:​ CRD42021278740). Twelve studies met eligibility criteria (n = 639) of patients receiving either PRP or CS. At short-term follow-up, a difference favored CS compared to PRP in baseline change for disability of arm, shoulder, and hand (DASH) score (MD = −5.08, 95% CI:​ −8.00, −2.15;​ p = 0.0007;​ I2 = 0%) and simple shoulder test (SST) (MD = 1.25, 95% CI:​ 0.33, 2.18;​ p = 0.008;​ I2 = 0%). At intermediate follow-up, a difference favored PRP to CS baseline change of the DASH score (MD = 3.41, 95% CI:​ 0.67, 6.15;​ p = 0.01;​ I2 = 0%). At medium-term, a difference favored PRP to CS baseline change of the American Shoulder and Elbow Surgeons Shoulder (ASES) score (MD = −4.42, 95% CI:​ −8.16, −0.67;​ p = 0.02;​ I2 = 0%). Both treatments achieved individual MCID for each score. Despite favoring CS at short-term follow-up and PRP at intermediate- and medium-term follow-up, functional and pain scores did not demonstrate any clinical difference between the two treatment modalities in management of rotator cuff disease at all follow-up periods.