The world number eight mustered just one break point in a one-sided contest as his disappointing season continued. Murray has struggled to replicate the form that saw him take the Wimbledon title last year and is currently without a coach after splitting from Ivan Lendl in March.
Colombia's Giraldo faces Roberto Bautista Agut in the last eight.
Earlier, defending champion Rafa Nadal showed glimpses of his best form and some rustiness as he beat Jarkko Nieminen 6-1 6-4 to advance to the quarter-finals.
The Spanish world number one is used to rolling over opponents on clay but this year he lost in the quarter-finals in Monte Carlo and Barcelona to dent his confidence ahead of his bid for a ninth French Open title.
The three-times champion started well and swept Nieminen aside in the first set with his powerful passing shots.
Nadal led 3-0 in the second set before Finn Nieminen, the world number 57, broke back and had break points in Nadal's next service game which he failed to take.
Nadal struggled with his timing but scraped through and next faces sixth seed Tomas Berdych who beat Grigor Dimitrov 3-6 6-3 6-2.
"At 6-1 and 3-0 I was playing at my best level since Monte Carlo but then I slowed down a bit and made some errors," Nadal told a news conference.
"I am working on finding my level and performance. Today I did what I had to do but I still need to be more consistent."
Barcelona Open champion Kei Nishikori of Japan reached the quarter-finals after beating eighth seed Milos Raonic 7-6 7-6, his eighth successive victory on clay.
Third round results
Santiago Giraldo (Colombia) beat 7-Andy Murray (Britain) 6-3 6-2
Roberto Bautista (Spain) beat Lukasz Kubot (Poland) 6-4 6-2
1-Rafa Nadal (Spain) beat Jarkko Nieminen (Finland) 6-1 6-4
10-Kei Nishikori (Japan) beat 8-Milos Raonic (Canada) 7-6(5) 7-6(5)
6-Tomas Berdych (Czech Republic) beat 12-Grigor Dimitrov (Bulgaria) 3-6 6-3 6-2
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