The computation of the Mittag-Leffler (ML) function with matrix arguments, and some applications in fractional calculus, are discussed. In general the evaluation of a scalar function in matrix arguments may require the computation of derivatives of possible high order depending on the matrix spectrum. Regarding the ML function, the numerical computation of its derivatives of arbitrary order is a completely unexplored topic; in this paper we address this issue and three different methods are tailored and investigated. The methods are combined together with an original derivatives balancing technique in order to devise an algorithm capable of providing high accuracy. The conditioning of the evaluation of matrix ML functions is also studied. The numerical experiments presented in the paper show that the proposed algorithm provides high accuracy, very often close to the machine precision. , avialable at https://doi.org/ 10.1007/s10915-018-0699-5. This work is supported under the GNCS-INdAM 2017 project "Analisi numerica per modelli descritti da operatori frazionari". arXiv:1804.04883v2 [math.NA] 1 Dec 2019where |δ 1 |, |δ 2 |, . . . , |δ J | < and terms proportional to O( 2 ) have been discarded. It is thus immediate to derive the following bound for the round-off errorThe order by which the terms c j are summed is relevant especially for the reliability of the above estimator; clearly, an ascending sorting of |c j | makes the estimate (16) more conservative and hence more useful for practical use. It is therefore advisable, especially in the more compelling cases (namely, for arguments z with large modulus and | arg(z)| > απ/2) to perform a preliminary sorting of the terms in (14) with respect to their modulus.An alternative estimate of the round-off error can be obtained after reformulating (15) asŜ J = S J + J j=1 S j δ j from which one can easily derive S J −Ŝ J ≤ J j=1