Despite

Despite,  like its cousin in spite of  is a preposition. That means it needs to be followed by a noun or by a verbal noun (=gerund).

😃Despite his efforts to understand her, she remained forever an enigma

😃In spite of his efforts to understand her, she remained forever an enigma

😧Despite he tried to unterstand her...

Alternatively, use the subordinators although/even though/while/whereas

😃Even though he made an effort to understand her...

😃Whereas he tied his best to understand her...

😃 While he made a great effort to understand her...